期刊
AUTOPHAGY
卷 16, 期 3, 页码 562-574出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2019.1634944
关键词
Mitochondrial membrane potential; mitochondrial topology; mitophagy; PINK1-PRKN; PARKIN; starvation
类别
资金
- National Key Research and Development Program of China [2018YFA0107100, 2017YFC1001602, 2017YFA0106300, 2017YFA0102900, 2016YFA0100300]
- Strategic Priorty Research Program of the Chinese Academy of Sciences [XDA16030505]
- Innovative Team Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR110103002]
- National Natural Science Foundation projects of China [U1601227, 31622037, 31631163001, 81570520, 31801168, 31701281, 31701106, 31601176, 31601088]
- Key Research Program of Frontier Sciences, CAS [QYZDB-SSW-SMC001]
- Open Research Program of Key Laboratory of Regenerative Biology, CAS [KLRB201808]
- Guangzhou Health Care and Cooperative Innovation Major Project [201704020218, 201604020009]
- Guangdong Province Science and Technology Program [2015TX01R047, 2014TQ01R559, 2014B020225006, 2017B020230005, 2015A020212031, 2017A020215056, 2017B030314056, 2018A030313825]
- Guangzhou Science and Technology Program [201707010178, 201807010067]
- CAS Youth Innovation Promotion Association
- Yangtse River Scholar Bonus Schemes
Selective elimination of mitochondria by autophagy is a critical strategy for a variety of physiological processes, including development, cell-fate determination and stress response. Although several mechanisms have been identified as responsible for selective degradation of mitochondria, such as the PINK1-PRKN/PARKIN- and receptor-dependent pathways, aspects of the mechanisms and particularly the principles underlying the selection process of mitochondria remain obscure. Here, we addressed a new selection strategy in which the selective elimination of mitochondria is dependent on organellar topology. We found that populations of mitochondria undergo different topological transformations under serum starvation, either swelling or forming donut shapes. Swollen mitochondria are associated with mitochondrial membrane potential dissipation and PRKN recruitment, which promote their selective elimination, while the donut topology maintains mitochondrial membrane potential and helps mitochondria resist autophagy. Mechanistic studies show that donuts resist autophagy even after depolarization through preventing recruitment of autophagosome receptors CALCOCO2/NDP52 and OPTN even after PRKN recruitment. Our results demonstrate topology-dependent, bifurcated mitochondrial recycling under starvation, that is swollen mitochondria undergo removal by autophagy, while donut mitochondria undergo fission and fusion cycles for reintegration. This study reveals a novel morphological selection for control of mitochondrial quality and quantity under starvation.
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