The Interplay Between Mitochondrial Dynamics and Mitophagy
Gilad Twig,Orian S. Shirihai +1 more
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TLDR
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.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. Antioxid. Redox Signal. 14, 1939–1951.read more
Citations
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The Roles of PINK1, Parkin and Mitochondrial Fidelity in Parkinson's Disease
TL;DR: Biochemical and genetic studies reveal that the products of two genes that are mutated in autosomal recessive parkinsonism, PINK1 and Parkin, normally work together in the same pathway to govern mitochondrial quality control, bolstering previous evidence that mitochondrial damage is involved in Parkinson's disease.
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The pathways of mitophagy for quality control and clearance of mitochondria.
TL;DR: The relevance of these pathways in neurons where defects in mitophagy have been implicated in neurodegeneration are discussed, in addition to the importance of identifying specific regulators ofMitophagy that ensure selective sequestration of mitochondria as cargo.
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Autophagy and apoptosis dysfunction in neurodegenerative disorders.
Saeid Ghavami,Shahla Shojaei,Behzad Yeganeh,Sudharsana R. Ande,Jaganmohan Reddy Jangamreddy,Maryam Mehrpour,Jonas Christoffersson,Wiem Chaabane,Adel Rezaei Moghadam,Hessam H. Kashani,Mohammad Hashemi,Ali Akbar Owji,Marek J. Łos +12 more
TL;DR: In this article, the authors provide a brief introduction to autophagy and apoptosis pathways focusing on the role of mitochondria and lysosomes, and discuss different ways that autophag and apoptotic modulation may be employed for therapeutic intervention during the maintenance of neurodegenerative disorders.
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Mitochondrial dynamics and mitochondrial quality control.
TL;DR: This review discusses the most recent progress on the molecular mechanisms and roles of mitochondrial fission/fusion and mitochondrial motility in mitophagy, and discusses multiple pathways leading to the quality control of mitochondria in addition to the traditionalMitophagy pathway under different conditions.
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Disturbed mitochondrial dynamics and neurodegenerative disorders
TL;DR: Interestingly, these cellular processes are also implicated in more-common complex neurodegenerative disorders, such as Alzheimer disease and Parkinson disease, indicating a common pathological thread and a close relationship with mitochondrial structure, function and localization.
References
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Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
TL;DR: It is shown that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells and this recruitment promotes autophagy of damaged mitochondria and implicate a failure to eliminate dysfunctional mitochondira in the pathogenesis of Parkinson's disease.
Journal ArticleDOI
Foxo Transcription Factors Induce the Atrophy-Related Ubiquitin Ligase Atrogin-1 and Cause Skeletal Muscle Atrophy
Marco Sandri,Claudia Sandri,Alexander Gilbert,Carsten Skurk,Elisa Calabria,Anne Picard,Kenneth Walsh,Stefano Schiaffino,Stewart H. Lecker,Alfred L. Goldberg +9 more
TL;DR: It is shown that in cultured myotubes undergoing atrophy, the activity of the PI3K/AKT pathway decreases, leading to activation of Foxo transcription factors and atrogin-1 induction.
Journal ArticleDOI
Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
Gilad Twig,Alvaro A. Elorza,Anthony J.A. Molina,Anthony J.A. Molina,Hibo Mohamed,Jakob D. Wikstrom,Gil Walzer,Linsey Stiles,Sarah E. Haigh,Steve Katz,Guy Las,Joseph Alroy,Min Wu,Bénédicte F. Py,Junying Yuan,Jude T. Deeney,Barbara E. Corkey,Orian S. Shirihai +17 more
TL;DR: Pulse chase and arrest of autophagy at the pre‐proteolysis stage reveal that fission followed by selective fusion segregates dysfunctional mitochondria and permits their removal by autophagic.
Journal ArticleDOI
The mitochondrial permeability transition pore and its role in cell death.
TL;DR: Current evidence that the pore complex is involved in outer-membrane rupture and release of these proteins during programmed cell death is reviewed, along with indications that transient pore opening may provoke 'accidental' apoptosis.
Journal ArticleDOI
PINK1 is selectively stabilized on impaired mitochondria to activate Parkin.
Derek P. Narendra,Seok Min Jin,Atsushi Tanaka,Der-Fen Suen,Clement A. Gautier,Jie Shen,Mark R. Cookson,Richard J. Youle +7 more
TL;DR: The authors suggest that PINK1 and Parkin form a pathway that senses damaged mitochondria and selectively targets them for degradation.