37 results match your criteria pathologic fission

Dexmedetomidine ameliorates endotoxin-induced acute lung injury in vivo and in vitro by preserving mitochondrial dynamic equilibrium through the HIF-1a/HO-1 signaling pathway.

Redox Biol 2021 Mar 21;41:101954. Epub 2021 Mar 21.

Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, China. Electronic address:

Increasing lines of evidence identified that dexmedetomidine (DEX) exerted protective effects against sepsis-stimulated acute lung injury via anti-inflammation, anti-oxidation and anti-apoptosis. However, the mechanisms remain unclear. Herein, we investigated whether DEX afforded lung protection by regulating the process of mitochondrial dynamics through the HIF-1a/HO-1 pathway in vivo and in vitro. Read More

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Relationship Between Mitochondrial Structure and Bioenergetics in Dermal Fibroblasts.

Front Cell Dev Biol 2020 17;8:610266. Epub 2020 Dec 17.

Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.

(PXE) is a genetic disease considered as a paradigm of ectopic mineralization disorders, being characterized by multisystem clinical manifestations due to progressive calcification of skin, eyes, and the cardiovascular system, resembling an age-related phenotype. Although fibroblasts do not express the pathogenic gene, nevertheless these cells are still under investigation because they regulate connective tissue homeostasis, generating the "arena" where cells and extracellular matrix components can promote pathologic calcification and where activation of pro-osteogenic factors can be associated to pathways involving mitochondrial metabolism. The aim of the present study was to integrate structural and bioenergenetic features to deeply investigate mitochondria from control and from PXE fibroblasts cultured in standard conditions and to explore the role of mitochondria in the development of the PXE fibroblasts' pathologic phenotype. Read More

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December 2020

The Noonan Syndrome Gene Controls Cardiovascular Function by Regulating Vesicular Trafficking.

Circ Res 2020 05 16;126(10):1379-1393. Epub 2020 Mar 16.

From the VIB-KU Leuven Center for Cancer Biology, Belgium (R.N.S., S.P., M.S., A.S., P.Z., N.C., M.F.B., B.L., A.A.S.).

Rationale: Noonan syndrome (NS) is one of the most frequent genetic disorders. Bleeding problems are among the most common, yet poorly defined complications associated with NS. A lack of consensus on the management of bleeding complications in patients with NS indicates an urgent need for new therapeutic approaches. Read More

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Identification of novel dynamin-related protein 1 (Drp1) GTPase inhibitors: Therapeutic potential of Drpitor1 and Drpitor1a in cancer and cardiac ischemia-reperfusion injury.

FASEB J 2020 01 2;34(1):1447-1464. Epub 2019 Dec 2.

Department of Medicine, Queen's University, Kingston, ON, Canada.

Mitochondrial fission is important in physiological processes, including coordination of mitochondrial and nuclear division during mitosis, and pathologic processes, such as the production of reactive oxygen species (ROS) during cardiac ischemia-reperfusion injury (IR). Mitochondrial fission is mainly mediated by dynamin-related protein 1 (Drp1), a large GTPase. The GTPase activity of Drp1 is essential for its fissogenic activity. Read More

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January 2020

ROCK1 induces dopaminergic nerve cell apoptosis via the activation of Drp1-mediated aberrant mitochondrial fission in Parkinson's disease.

Exp Mol Med 2019 10 2;51(10):1-13. Epub 2019 Oct 2.

Department of Pharmacy, The Second Affiliated Hospital of Army Medical University, 400037, Chongqing, China.

Dopamine deficiency is mainly caused by apoptosis of dopaminergic nerve cells in the substantia nigra of the midbrain and the striatum and is an important pathologic basis of Parkinson's disease (PD). Recent research has shown that dynamin-related protein 1 (Drp1)-mediated aberrant mitochondrial fission plays a crucial role in dopaminergic nerve cell apoptosis. However, the upstream regulatory mechanism remains unclear. Read More

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October 2019

Mdivi-1 Protects CD4 T Cells against Apoptosis via Balancing Mitochondrial Fusion-Fission and Preventing the Induction of Endoplasmic Reticulum Stress in Sepsis.

Mediators Inflamm 2019 16;2019:7329131. Epub 2019 May 16.

Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Apoptosis of CD4 T cells plays a central role in the progression of sepsis because it is associated with subsequent immunosuppression and the lack of specific treatment. Thus, developing therapeutic strategies to attenuate the apoptosis of CD4 T cells in sepsis is critical. Several studies have demonstrated that Mdivi-1, which is a selective inhibitor of the dynamin-related protein 1 (Drp1), attenuates apoptosis of myocardial cells and neurons during various pathologic states. Read More

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January 2020

Mitochondria as playmakers of apoptosis, autophagy and senescence.

Semin Cell Dev Biol 2020 02 27;98:139-153. Epub 2019 Jun 27.

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy. Electronic address:

Mitochondria are the key energy-producing organelles and cellular source of reactive species. They are responsible for managing cell life and death by a balanced homeostasis passing through a network of structures, regulated principally via fission and fusion. Herein we discuss about the most advanced findings considering mitochondria as dynamic biophysical systems playing compelling roles in the regulation of energy metabolism in both physiologic and pathologic processes controlling cell death and survival. Read More

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February 2020

Drp1/Fis1 interaction mediates mitochondrial dysfunction in septic cardiomyopathy.

J Mol Cell Cardiol 2019 05 11;130:160-169. Epub 2019 Apr 11.

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Mitochondrial dysfunction is a key contributor to septic cardiomyopathy. Although recent literature implicates dynamin related protein 1 (Drp1) and its mitochondrial adaptor fission 1 (Fis1) in the development of pathologic fission and mitochondrial failure in neurodegenerative disease, little is known about the role of Drp1/Fis1 interaction in the context of sepsis-induced cardiomyopathy. Our study tests the hypothesis that Drp1/Fis1 interaction is a major driver of sepsis-mediated pathologic fission, leading to mitochondrial dysfunction in the heart. Read More

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Reactive species-induced microvascular dysfunction in ischemia/reperfusion.

Free Radic Biol Med 2019 05 5;135:182-197. Epub 2019 Mar 5.

Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, 1 Hospital Drive, Columbia, MO 65212, USA; Dalton Cardiovascular Research Center, University of Missouri, 134 Research Park Drive, Columbia, MO 65211, USA. Electronic address:

Vascular endothelial cells line the inner surface of the entire cardiovascular system as a single layer and are involved in an impressive array of functions, ranging from the regulation of vascular tone in resistance arteries and arterioles, modulation of microvascular barrier function in capillaries and postcapillary venules, and control of proinflammatory and prothrombotic processes, which occur in all segments of the vascular tree but can be especially prominent in postcapillary venules. When tissues are subjected to ischemia/reperfusion (I/R), the endothelium of resistance arteries and arterioles, capillaries, and postcapillary venules become dysfunctional, resulting in impaired endothelium-dependent vasodilator and enhanced endothelium-dependent vasoconstrictor responses along with increased vulnerability to thrombus formation, enhanced fluid filtration and protein extravasation, and increased blood-to-interstitium trafficking of leukocytes in these functionally distinct segments of the microcirculation. The number of capillaries open to flow upon reperfusion also declines as a result of I/R, which impairs nutritive perfusion. Read More

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Multi-targeted Effect of Nicotinamide Mononucleotide on Brain Bioenergetic Metabolism.

Neurochem Res 2019 Oct 19;44(10):2280-2287. Epub 2019 Jan 19.

Veterans Affairs Maryland Health Care System, 10 North Greene Street, Baltimore, MD, 21201, USA.

Dysfunctions in NAD metabolism are associated with neurodegenerative diseases, acute brain injury, diabetes, and aging. Loss of NAD levels results in impairment of mitochondria function, which leads to failure of essential metabolic processes. Strategies to replenish depleted NAD pools can offer significant improvements of pathologic states. Read More

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October 2019

Mitophagy, a potential therapeutic target for stroke.

J Biomed Sci 2018 Nov 30;25(1):87. Epub 2018 Nov 30.

Heilongjiang University Of Chinese Medicine, Harbin, 150040, Heilongjiang province, China.

Mitochondria autophagy, termed as mitophagy, is a mechanism of specific autophagic elimination of mitochondria. Mitophagy controls the quality and the number of mitochondria, eliminating dysfunctional or excessive mitochondria that can generate reactive oxygen species (ROS) and cause cell death. Mitochondria are centrally implicated in neuron and tissue injury after stroke, due to the function of supplying adenosine triphosphate (ATP) to the tissue, regulating oxidative metabolism during the pathologic process, and contribution to apoptotic cell death after stroke. Read More

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November 2018

FOXO1 inhibition potentiates endothelial angiogenic functions in diabetes via suppression of ROCK1/Drp1-mediated mitochondrial fission.

Biochim Biophys Acta Mol Basis Dis 2018 Jul 11;1864(7):2481-2494. Epub 2018 Apr 11.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China; Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address:

Diabetes-induced endothelial cell (EC) dysfunction and neovascularization impairment constitute vascular complications with limited treatment regimens. Transcription factor FOXO1 is a key angiogenic regulator and plays a pathologic role in progression of diabetes. The present study was designed to determine the involvement of FOXO1 in impaired EC function and post-ischemic neovascularization in diabetes and investigate underlying mechanisms. Read More

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Mitochondrial Fission Promotes the Continued Clearance of Apoptotic Cells by Macrophages.

Cell 2017 Oct 21;171(2):331-345.e22. Epub 2017 Sep 21.

Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Department of Physiology, Columbia University, New York, NY 10032, USA. Electronic address:

Clearance of apoptotic cells (ACs) by phagocytes (efferocytosis) prevents post-apoptotic necrosis and dampens inflammation. Defective efferocytosis drives important diseases, including atherosclerosis. For efficient efferocytosis, phagocytes must be able to internalize multiple ACs. Read More

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October 2017

Significance of Mitochondrial Protein Post-translational Modifications in Pathophysiology of Brain Injury.

Transl Stroke Res 2018 06 21;9(3):223-237. Epub 2017 Sep 21.

Veterans Affairs Maryland Health Center System, 10 North Greene Street, Baltimore, MD, 21201, USA.

Mitochondria are complex organelles that undergo constant fusion and fission in order to adapt to the ever-changing cellular environment. The fusion/fission proteins, localized in the inner and outer mitochondrial membrane, play critical roles under pathological conditions such as acute brain injury and neurodegenerative diseases. Post-translational modifications of these proteins tightly regulate their function and activity, ultimately impacting mitochondrial dynamics and their efficiency to generate ATP. Read More

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Astragaloside IV ameliorates diabetic nephropathy by modulating the mitochondrial quality control network.

PLoS One 2017 2;12(8):e0182558. Epub 2017 Aug 2.

Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.

The aim of this study was to investigate the effect and possible mechanism of Astragaloside IV (AS-IV) on retarding the progression of diabetic nephropathy (DN) in a type 2 diabetic animal model, db/db mice. Eight-week-old male db/db diabetic mice and their nondiabetic littermate control db/m mice were used in the present study. AS-IV was administered to the db/db mice by adding it to standard feed at a dose of 1g/kg for 12 weeks. Read More

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September 2017

Ginsenoside Rg3 restores hepatitis C virus-induced aberrant mitochondrial dynamics and inhibits virus propagation.

Hepatology 2017 09 1;66(3):758-771. Epub 2017 Aug 1.

Department of Medicine, University of California, San Diego, La Jolla, CA.

Hepatitis C virus (HCV) alters mitochondrial dynamics associated with persistent viral infection and suppression of innate immunity. Mitochondrial dysfunction is also a pathologic feature of direct-acting antiviral (DAA) treatment. Despite the high efficacy of DAAs, their use in treating patients with chronic hepatitis C in interferon-sparing regimens occasionally produces undesirable side effects such as fatigue, migraine, and other conditions, which may be linked to mitochondrial dysfunction. Read More

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September 2017

Mitochondrial NUDIX hydrolases: A metabolic link between NAD catabolism, GTP and mitochondrial dynamics.

Neurochem Int 2017 Oct 14;109:193-201. Epub 2017 Mar 14.

Veterans Affairs Maryland Health Center System, 10 North Greene Street, Baltimore, MD 21201, United States; Department of Anesthesiology and the Center for Shock, Trauma, and Anesthesiology Research (S.T.A.R.), United States. Electronic address:

NAD catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Read More

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October 2017

Heme Oxygenase-1/Carbon Monoxide-regulated Mitochondrial Dynamic Equilibrium Contributes to the Attenuation of Endotoxin-induced Acute Lung Injury in Rats and in Lipopolysaccharide-activated Macrophages.

Anesthesiology 2016 12;125(6):1190-1201

From the Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, China (J.Y., J.S., D.W., S.D., Y.Z., M.W., L.G.); Department of Intensive Care Medicine, Fourth Center Clinical College of Tianjin Medical University, Tianjin, China (Q.F.); and Department of Pharmacology, Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Tianjin, China (D.L.).

Background: Sepsis-associated acute lung injury remains the major cause of mortality in critically ill patients and is characterized by marked oxidative stress and mitochondrial dysfunction. Mitochondrial dynamics are indispensable for functional integrity. Additionally, heme oxygenase (HO)-1/carbon monoxide conferred cytoprotection against end-organ damage during endotoxic shock. Read More

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December 2016

The Role of BCL-2 Family Members in Acute Kidney Injury.

Steven C Borkan

Semin Nephrol 2016 05;36(3):237-50

Evans Biomedical Research Center, Boston University Medical Center, Boston, MA. Electronic address:

B-cell lymphoma 2 (BCL-2) family proteins gather at the biologic cross-roads of renal cell survival: the outer mitochondrial membrane. Despite shared sequence and structural features, members of this conserved protein family constantly antagonize each other in a life-and-death battle. BCL-2 members innocently reside within renal cells until activated or de-activated by physiologic stresses caused by common nephrotoxins, transient ischemia, or acute glomerulonephritis. Read More

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OPA1 processing in cell death and disease - the long and short of it.

J Cell Sci 2016 06 17;129(12):2297-306. Epub 2016 May 17.

Institute of Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Center for Molecular Medicine (CMMC), University of Cologne, Cologne 50931, Germany

The regulation of mitochondrial dynamics by the GTPase OPA1, which is located at the inner mitochondrial membrane, is crucial for adapting mitochondrial function and preserving cellular health. OPA1 governs the delicate balance between fusion and fission in the dynamic mitochondrial network. A disturbance of this balance, often observed under stress and pathologic conditions, causes mitochondrial fragmentation and can ultimately result in cell death. Read More

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Dynamin-Related Protein 1 Deficiency Improves Mitochondrial Fitness and Protects against Progression of Diabetic Nephropathy.

J Am Soc Nephrol 2016 09 29;27(9):2733-47. Epub 2016 Jan 29.

Section of Nephrology, Department of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas; Pharmacology, Baylor College of Medicine, Houston, Texas; and

Mitochondrial fission has been linked to the pathogenesis of diabetic nephropathy (DN). However, how mitochondrial fission affects progression of DN in vivo is unknown. Here, we report the effect of conditional podocyte-specific deletion of dynamin-related protein 1 (Drp1), an essential component of mitochondrial fission, on the pathogenesis and progression of DN. Read More

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September 2016

Pathological characteristics of liver biopsies in eight patients with hepatic epithelioid hemangioendothelioma.

Int J Clin Exp Pathol 2015 1;8(9):11015-23. Epub 2015 Sep 1.

Department of Pathology, Beijing Youan Hospital, Capital Medical University Beijing 100069, China.

We aim to investigate the pathological characteristics of liver biopsies and their implications for the prognosis of hepatic epithelioid hemangioendothelioma (HEHE). Clinical data of eight patients (5 male, 3 female) with HEHE were analyzed retrospectively. Expression of CD34, FVIII, AE1/AE3, Hepa-par1, GPC3, CK19 and the proliferation index marker Ki-67 were determined by immunohistochemical staining. Read More

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September 2016

Visual cortex hyperexcitability in migraine in response to sound-induced flash illusions.

Neurology 2015 May 17;84(20):2057-61. Epub 2015 Apr 17.

From the Department of Experimental Biomedicine and Clinical Neuroscience (F.B., G.C., S.M., P.P., R.B., B.F.), University of Palermo; Department of Psychology (N.B., G.V.), University of Milano Bicocca, Milano; Laboratory of Neuropsychology (N.B., G.V.), IRCSS Istituto Auxologico Italiano, Milano; and Milan Center for Neuroscience (N.B., G.V.), Milano, Italy.

Objective: Sound-induced flash illusions depend on visual cortical excitability. In this study, we explored whether sound-induced flash illusions are perceived differently in migraine, a condition associated with pathologic cortical hyperexcitability.

Methods: Sound-induced flash illusions were examined in 59 migraine patients (mean age = 32 ± 16 years; 36 females), 32 without aura and 27 with aura, and in 24 healthy controls (mean age = 42 ± 17 years; 16 females). Read More

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Disorders of phospholipid metabolism: an emerging class of mitochondrial disease due to defects in nuclear genes.

Front Genet 2015 3;6. Epub 2015 Feb 3.

Department of Physiology, School of Medicine, Johns Hopkins University Baltimore, MD, USA.

The human nuclear and mitochondrial genomes co-exist within each cell. While the mitochondrial genome encodes for a limited number of proteins, transfer RNAs, and ribosomal RNAs, the vast majority of mitochondrial proteins are encoded in the nuclear genome. Of the multitude of mitochondrial disorders known to date, only a fifth are maternally inherited. Read More

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February 2015

Regulation of mitochondrial morphology by positive feedback interaction between PKCδ and Drp1 in vascular smooth muscle cell.

J Cell Biochem 2015 Apr;116(4):648-60

Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University Health System, Seodaemun-gu, Seoul, 120-752, Republic of Korea.

Dynamin-related protein-1 (Drp1) plays a critical role in mitochondrial fission which allows cell proliferation and Mdivi-1, a specific small molecule Drp1 inhibitor, is revealed to attenuate proliferation. However, few molecular mechanisms-related to Drp1 under stimulus for restenosis or atherosclerosis have been investigated in vascular smooth muscle cells (vSMCs). Therefore, we hypothesized that Drp1 inhibition can prevent vascular restenosis and investigated its regulatory mechanism. Read More

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Relocation of p25α/tubulin polymerization promoting protein from the nucleus to the perinuclear cytoplasm in the oligodendroglia of sporadic and COQ2 mutant multiple system atrophy.

Acta Neuropathol Commun 2014 Sep 11;2:136. Epub 2014 Sep 11.

p25α/tubulin polymerization promoting protein (TPPP) is an oligodendroglial protein that plays crucial roles including myelination, and the stabilization of microtubules. In multiple system atrophy (MSA), TPPP is suggested to relocate from the myelin sheath to the oligodendroglial cell body, before the formation of glial cytoplasmic inclusions (GCIs), the pathologic hallmark of MSA. However, much is left unknown about the re-distribution of TPPP in MSA. Read More

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September 2014

PGC1α-mediated mitofusin-2 deficiency in female rats and humans with pulmonary arterial hypertension.

Am J Respir Crit Care Med 2013 Apr;187(8):865-78

Section of Cardiology, Department of Medicine, University of Chicago, Chicago, IL, USA.

Rationale: Pulmonary arterial hypertension (PAH) is a lethal, female-predominant, vascular disease. Pathologic changes in PA smooth muscle cells (PASMC) include excessive proliferation, apoptosis-resistance, and mitochondrial fragmentation. Activation of dynamin-related protein increases mitotic fission and promotes this proliferation-apoptosis imbalance. Read More

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Mitochondrial fission induces glycolytic reprogramming in cancer-associated myofibroblasts, driving stromal lactate production, and early tumor growth.

Oncotarget 2012 Aug;3(8):798-810

The Jefferson Stem Cell Biology and Regenerative Medicine Center, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.

Recent studies have suggested that cancer cells behave as metabolic parasites, by inducing oxidative stress in adjacent normal fibroblasts. More specifically, oncogenic mutations in cancer cells lead to ROS production and the "secretion" of hydrogen peroxide species. Oxidative stress in stromal fibroblasts then induces their metabolic conversion into cancer-associated fibroblasts. Read More

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Transgenic control of mitochondrial fission induces mitochondrial uncoupling and relieves diabetic oxidative stress.

Diabetes 2012 Aug 14;61(8):2093-104. Epub 2012 Jun 14.

Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.

Mitochondria are the essential eukaryotic organelles that produce most cellular energy. The energy production and supply by mitochondria appear closely associated with the continuous shape change of mitochondria mediated by fission and fusion, as evidenced not only by the hereditary diseases caused by mutations in fission/fusion genes but also by aberrant mitochondrial morphologies associated with numerous pathologic insults. However, how morphological change of mitochondria is linked to their energy-producing activity is poorly understood. Read More

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Microvesicles: mediators of extracellular communication during cancer progression.

J Cell Sci 2010 May;123(Pt 10):1603-11

Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556-0369, USA.

Microvesicles are generated by the outward budding and fission of membrane vesicles from the cell surface. Recent studies suggest that microvesicle shedding is a highly regulated process that occurs in a spectrum of cell types and, more frequently, in tumor cells. Microvesicles have been widely detected in various biological fluids including peripheral blood, urine and ascitic fluids, and their function and composition depend on the cells from which they originate. Read More

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