How autophagy eats large mitochondria: Autophagosome formation coupled with mitochondrial fragmentation

Autophagy
Shun-Ichi Yamashita, Tomotake Kanki

Abstract

Mitochondrial autophagy (mitophagy) is thought to be a multi-step pathway wherein mitochondria are first divided into small fragments, which are subsequently recognized by the phagophore. DNM1L (dynamin 1 like) plays a pivotal role in mitochondrial division; however, its role in mitophagy remains controversial. In our recent study, we examined the contribution of DNM1L to mitophagy and showed that mitophagy and mitochondrial division occur even in DNM1L-defective cells. Furthermore, time-lapse imaging of mitophagy showed that DNM1L-independent mitochondrial division occurs concomitantly with autophagosome formation. Upstream factors of autophagosome formation, i.e., RB1CC1/FIP200, ATG14, and WIPIs, are required for mitochondrial division, whereas ATG5 and ATG3 are dispensable. These results indicate that a portion of the tubular mitochondria is first recognized and then divided into small fragments by a phagophore-mediated event, independently of DNM1L. This autophagic process suggests that autophagy has the potential to degrade substrates larger than autophagosomes.

Citations

Sep 5, 2017·Cells·Yanfang ChenRenaud Legouis
Dec 31, 2019·Oxidative Medicine and Cellular Longevity·Alejandra Guillermina Miranda-DíazFermín Paul Pacheco-Moisés
Nov 30, 2019·Oxidative Medicine and Cellular Longevity·Ne N WuJun Ren
Nov 12, 2020·Experimental Biology and Medicine·Xiaorong FengY James Kang
Mar 5, 2021·Developmental Cell·Matthew Yoke Wui NgAnne Simonsen
Mar 15, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lizhuo WangJialin Gao
Sep 9, 2020·Journal of Molecular Biology·Hannah K MargolisMichael J Ragusa
Aug 28, 2021·International Journal of Molecular Sciences·Diana SalnikovaAlexander Orekhov
Dec 11, 2021·Journal of Cellular Biochemistry·Sante Roperto

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Methods Mentioned

BETA
electron microscopy

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