Journal
REDOX BIOLOGY
Volume 2, Issue -, Pages 749-754Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.redox.2014.06.004
Keywords
Micromitophagy; Mitochondria-derived vesicles; Mitophagy; Nutrient deprivation; Photodamage; Preautophagic structure
Categories
Funding
- National Institutes of Health [2 R01 DK37034, 1 R01 DK073336, P30 CA138313, P20 GM103542, C06 RR015455]
- Russian Federation [14.Z50.31.0028]
- NATIONAL CANCER INSTITUTE [P30CA138313] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR015455] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R56DK037034, R37DK037034, R01DK037034, R01DK073336] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM103542] Funding Source: NIH RePORTER
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Mitophagy (mitochondrial autophagy), which removes damaged, effete and superfluous mitochondria, has several distinct variants. In Type 1 mitophagy occurring during nutrient deprivation, preautophagic structures (PAS) grow into cup-shaped phagophores that surround and sequester individual mitochondria into mitophagosomes, a process requiring phosphatidylinositol-3-kinase (PI3K) and often occurring in coordination with mitochondrial fission. After sequestration, the outer compartment of the mitophagosome acidifies, followed by mitochondrial depolarization and ultimately hydrolytic digestion in lysosomes. Mitochondrial damage stimulates Type 2 mitophagy. After photodamage to single mitochondria, depolarization occurs followed by decoration and then coalescence of autophagic LC3-containing structures on mitochondrial surfaces. Vesicular acidification then occurs. By contrast to Type 1 mitophagy, PI3K inhibition does not block Type 2 mitophagy. Further, Type 2 mitophagy is not associated with phagophore formation or mitochondrial fission. A third form of self-eating of mitochondria is formation of mitochondria-derived vesicles (MDVs) enriched in oxidized mitochondrial proteins that bud off and transit into multivesicular bodies. Topologically, the internalization of MDV by invagination of the surface of multivesicular bodies followed by vesicle scission into the lumen is a form of microautophagy, or micromitophagy (Type 3 mitophagy). Cell biological distinctions are the basis for these three types of mitophagy. Future studies are needed to better characterize the molecular and biochemical differences between Types 1, 2 and 3 mitophagy. (C) 2014 The Authors. Published by Elsevier B.V.
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