TY - JOUR
T1 - Evolving and expanding the roles of mitophagy as a homeostatic and pathogenic process
AU - Gustafsson, Åsa B.
AU - Dorn, Gerald W.
N1 - Funding Information:
Å. B. Gustafsson is supported by an American Heart Association Established Investigator Award and by National Institutes of Health (NIH) Grants R21AG052280, R01HL132300, R01HL138560, and P01HL085577. G. W. Dorn II is supported by NIH/National Heart, Lung, and Blood Institute Grant R35 135736.
Publisher Copyright:
© 2019 the American Physiological Society.
PY - 2019/1
Y1 - 2019/1
N2 - The central functions fulfilled by mitochondria as both energy generators essential for tissue homeostasis and gateways to programmed apoptotic and necrotic cell death mandate tight control over the quality and quantity of these ubiquitous endosymbiotic organelles. Mitophagy, the targeted engulfment and destruction of mitochondria by the cellular autophagy apparatus, has conventionally been considered as the mechanism primarily responsible for mitochondrial quality control. However, our understanding of how, why, and under what specific conditions mitophagy is activated has grown tremendously over the past decade. Evidence is accumulating that nonmitophagic mitochondrial quality control mechanisms are more important to maintaining normal tissue homeostasis whereas mitophagy is an acute tissue stress response. Moreover, previously unrecognized mitophagic regulation of mitochondrial quantity control, metabolic reprogramming, and cell differentiation suggests that the mechanisms linking genetic or acquired defects in mitophagy to neurodegenerative and cardiovascular diseases or cancer are more complex than simple failure of normal mitochondrial quality control. Here, we provide a comprehensive overview of mitophagy in cellular homeostasis and disease and examine the most revolutionary concepts in these areas. In this context, we discuss evidence that atypical mitophagy and nonmitophagic pathways play central roles in mitochondrial quality control, functioning that was previously considered to be the primary domain of mitophagy.
AB - The central functions fulfilled by mitochondria as both energy generators essential for tissue homeostasis and gateways to programmed apoptotic and necrotic cell death mandate tight control over the quality and quantity of these ubiquitous endosymbiotic organelles. Mitophagy, the targeted engulfment and destruction of mitochondria by the cellular autophagy apparatus, has conventionally been considered as the mechanism primarily responsible for mitochondrial quality control. However, our understanding of how, why, and under what specific conditions mitophagy is activated has grown tremendously over the past decade. Evidence is accumulating that nonmitophagic mitochondrial quality control mechanisms are more important to maintaining normal tissue homeostasis whereas mitophagy is an acute tissue stress response. Moreover, previously unrecognized mitophagic regulation of mitochondrial quantity control, metabolic reprogramming, and cell differentiation suggests that the mechanisms linking genetic or acquired defects in mitophagy to neurodegenerative and cardiovascular diseases or cancer are more complex than simple failure of normal mitochondrial quality control. Here, we provide a comprehensive overview of mitophagy in cellular homeostasis and disease and examine the most revolutionary concepts in these areas. In this context, we discuss evidence that atypical mitophagy and nonmitophagic pathways play central roles in mitochondrial quality control, functioning that was previously considered to be the primary domain of mitophagy.
UR - http://www.scopus.com/inward/record.url?scp=85058605077&partnerID=8YFLogxK
U2 - 10.1152/physrev.00005.2018
DO - 10.1152/physrev.00005.2018
M3 - Article
C2 - 30540226
AN - SCOPUS:85058605077
VL - 99
SP - 853
EP - 892
JO - Physiological Reviews
JF - Physiological Reviews
SN - 0031-9333
IS - 1
ER -