The interplay between mitochondrial dynamics and mitophagy. Antioxid Redox Signal

Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Antioxidants & Redox Signaling (Impact Factor: 7.67). 12/2010; 14(10):1939-51. DOI: 10.1089/ars.2010.3779
Source: PubMed

ABSTRACT Mitochondrial dynamics and mitophagy are recognized as two critical processes underlying mitochondrial homeostasis. Morphological and bioenergetic characterization of the life cycle of an individual mitochondrion reveals several points where fusion, fission, and mitophagy interact. Mitochondrial fission can produce an impaired daughter unit that will be targeted by the autophagic machinery. Mitochondrial fusion, on the other hand, may serve to dilute impaired respiratory components and thereby prevent their removal. The inverse dependency of fusion and mitophagy on membrane potential allows them to act as complementary rather than competitive fates of the daughter mitochondrion after a fission event. We discuss the interplay between mitochondrial dynamics and mitophagy in different tissues and in different disease models under both stress-induced and steady-state conditions.

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Available from: Gilad Twig, Aug 28, 2015
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    • "Mitochondria can change their shape, size and inner membrane structure in a dynamic fashion, and the mitochondria of a single cell do not function in isolation, but form a complex reticulum whose morphology undergoes continuous cycles of fusion and fission (Twig and Shirihai 2011). These opposing processes determine the architecture of the entire mitochondrial population for which a strict control of such events is essential for maintaining the metabolic function of mitochondria. "
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    ABSTRACT: Parkinson's disease is a common, adult-onset neurodegenerative disorder whose pathogenesis is still under intense investigation. Substantial evidence from postmortem human brain tissue, genetic- and toxin-induced animal and cellular models indicates that mitochondrial dysfunction plays a central role in the pathophysiology of the disease. This review discusses our current understanding of Parkinson's disease-related mitochondrial dysfunction, including bioenergetic defects, mitochondrial DNA alterations, altered mitochondrial dynamics, activation of mitochondrial-dependent programmed cell death, and perturbations in mitochondrial tethering to the endoplasmic reticulum. Whether a primary or secondary event, mitochondrial dysfunction holds promise as a potential therapeutic target to halt the progression of neurodegeneration in Parkinson's disease. © The Author(s) 2015.
    The Neuroscientist 03/2015; DOI:10.1177/1073858415574600 · 7.62 Impact Factor
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    • "The mitochondrial fission can facilitate removal of damaged mitochondrial components by partitioning them to a daughter mitochondrion that can then be targeted and removed by mitophagy [56]. Disruption of the mitochondrial quality control mechanisms associated with the interplay between mitochondrial dynamics and mitophagy in different tissues [56] has also been linked to various cardiac diseases [7]. Emerging key players in the regulation of mammalian mitophagy are the serine/threonine kinase PTEN-induced putative kinase 1 (Pink1) and the E3 ubiquitin ligase Parkin, which selectively promote the degradation of impaired mitochondria [57] (Fig. 1B). "
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    ABSTRACT: Diabetic cardiomyopathy (DCM) is a common consequence of longstanding type 2 diabetes mellitus (T2DM) and encompasses structural, morphological, functional, and metabolic abnormalities in the heart. Myocardial energy metabolism depends on mitochondria, which must generate sufficient ATP to meet the high energy demands of the myocardium. Dysfunctional mitochondria are involved in the pathophysiology of diabetic heart disease. A large body of evidence implicates myocardial insulin resistance in the pathogenesis of DCM. Recent studies show that insulin signaling influences myocardial energy metabolism by impacting cardiomyocyte mitochondrial dynamics and function under physiological conditions. However, comprehensive understanding of molecular mechanisms linking insulin signaling and changes in the architecture of the mitochondrial network in diabetic cardiomyopathy is lacking. This review summarizes our current understanding of how defective insulin signaling impacts cardiac function in diabetic cardiomyopathy and discusses the potential role of mitochondrial dynamics. Copyright © 2015 Elsevier B.V. All rights reserved.
    Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 02/2015; 1853(5). DOI:10.1016/j.bbamcr.2015.02.005 · 5.30 Impact Factor
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    • "This increased fusion activity is presumably facilitated by a betterpreserved mitochondrial mobility. As a result, elongated mitochondria are more resistant to rotenone toxicity through maintaining a mitochondrial network for efficient repair of damaged mitochondria (Twig and Shirihai, 2011). Indeed, we show in Drosophila S2R + cells that hUCP2 activity renders those cells more resistant to rotenone-induced mitochondrial depolarization, a strong indication of mitochondrial health. "
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