Cell & Bioscience | |
Mitochondria directly donate their membrane to form autophagosomes during a novel mechanism of parkin-associated mitophagy | |
Robert Clarke2  David D Roberts3  Pamela AG Clarke2  Mones Abu-Asab1  David R Soto-Pantoja3  Katherine L Cook2  | |
[1] Immunopathology Section, Laboratory of Immunology, National Eye Institute National Institutes of Health, Bethesda, MD 20892, USA;Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA;Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA | |
关键词: Estrogen receptor-α; Imatinib; Fulvestrant; Antiestrogen resistance; Parkin; Mitophagy; Autophagy; Mitochondria; Breast cancer; | |
Others : 790959 DOI : 10.1186/2045-3701-4-16 |
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received in 2013-11-13, accepted in 2014-02-06, 发布年份 2014 | |
【 摘 要 】
Background
Autophagy (macroautophagy), a cellular process of “self-eating”, segregates damaged/aged organelles into vesicles, fuses with lysosomes, and enables recycling of the digested materials. The precise origin(s) of the autophagosome membrane is unclear and remains a critical but unanswered question. Endoplasmic reticulum, mitochondria, Golgi complex, and the plasma membrane have been proposed as the source of autophagosomal membranes.
Findings
Using electron microscopy, immunogold labeling techniques, confocal microscopy, and flow cytometry we show that mitochondria can directly donate their membrane material to form autophagosomes. We expand upon earlier studies to show that mitochondria donate their membranes to form autophagosomes during basal and drug-induced autophagy. Moreover, electron microscopy and immunogold labeling studies show the first physical evidence of mitochondria forming continuous structures with LC3-labeled autophagosomes. The mitochondria forming these structures also stain positive for parkin, indicating that these mitochondrial-formed autophagosomes represent a novel mechanism of parkin-associated mitophagy.
Conclusions
With the on-going debate regarding autophagosomal membrane origin, this report demonstrates that mitochondria can donate membrane materials to form autophagosomes. These structures may also represent a novel form of mitophagy where the mitochondria contribute to the formation of autophagosomes. This novel form of parkin-associated mitophagy may be a more efficient bio-energetic process compared with de novo biosynthesis of a new membrane, particularly if the membrane is obtained, at least partly, from the organelle being targeted for later degradation in the mature autolysosome.
【 授权许可】
2014 Cook et al.; licensee BioMed Central Ltd.
【 预 览 】
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