title: Bit-by-bit autophagic removal of parkin-labelled mitochondria.
abstract: Eukaryotic cells maintain mitochondrial integrity through mitophagy, an autophagic process by which dysfunctional mitochondria are selectively sequestered into double-layered membrane structures, termed phagophores, and delivered to lysosomes for degradation. Here we show that small fragments of parkin-labelled mitochondria at omegasome-marked sites are engulfed by autophagic membranes one at a time. Using a light-activation scheme to impair long mitochondrial tubules, we demonstrate that sites undergoing bit-by-bit mitophagy display preferential ubiquitination, and are situated where parkin-labelled mitochondrial tubules and endoplasmic reticulum intersect. Our observations suggest contact regions between the endoplasmic reticulum and impaired mitochondria are initiation sites for local LC3 recruitment and mitochondrial remodelling that support bit-by-bit, parkin-mediated mitophagy. These results help in understanding how cells manage to fit large and morphologically heterogeneous mitochondria into micron-sized autophagic membranes during mitophagy.
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Yang
authors.forename: Wei Yuan
authors.initials: WY
authors.lastname: Yang
mesh_terms: D000818:Animals; D001343:Autophagy; D019556:COS Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D063306:Mitophagy; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D013194:Staining and Labeling; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D046988:Proteasome Endopeptidase Complex