Mitochondria supply membranes for autophagosome biogenesis during starvation

By D. Hailey, P. Kim, Prasanna Satpute-Krishnan, Angelika S. Rambold, K. Mitra, Rachid Sougrat, Jennifer Lippincott-Schwartz. Cell, 2010

1,406 citations recorded by the source corpus.

Starvation-induced autophagosomes engulf cytosol and/or organelles and deliver them to lysosomes for degradation, thereby re-supplying depleted nutrients. Despite advances in understanding the molecular basis of this process, the membrane origin of autophagosomes remains unclear. Here, we demonstrate that, in starved cells, autophagosomes are derived from the outer membranes of mitochondria. In time-lapse movies, the early autophagosomal marker, mApg5, transiently localizes to punctae on the surface of mitochondria, followed by the late autophagosomal marker, LC3. A unique tail-anchored outer mitochondrial membrane protein, but not other outer nor inner mitochondrial membrane proteins, labels autophagosomes and diffuses into newly forming autophagosomes from mitochondria. The fluorescent lipid, NBD-PS (which converts to PE in mitochondria) transfers from mitochondria to autophagosomes in starved cells. In addition, when mitochondria/ER connections are perturbed by loss of mitofusin2, starvation-induced autophagosomes do not form. Mitochondria thus play a central role in starvation-induced autophagy, serving as membrane source of autophagosomes.

Subfields: Cell Biology, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/68bb4068ccc5fb4f8f6408e677cddd852ffc6188

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Citations in the corpus

The regulation of autophagy – unanswered questions (2011, background): “What are the mechanisms of phagophore expansion and autophagosome formation? As almost all intracellular organelles, such as the ER, Golgi, endosomes, mitochondria and the plasma membrane have been implicated in the formation of autophagosomes (Geng et al., 2010; Hailey et al., 2010; Luo et al., 200”
The Interplay Between Mitochondrial Dynamics and Mitophagy (2011, background): “Mfn2 KO MEFs Inhibition of autophagy (36) No specific tests for mitophagy”
Deacetylation of nuclear LC3 drives autophagy initiation under starvation. (2015, background): “Alternatively, nuclear LC3 may serve as a reserve for the cytoplasmic pool and shifts to the cytosol when soluble cytoplasmic LC3 is transformed to the lipidated typeand incorporated into autophagic membranes (Drake et al., 2010; Hailey et al., 2010).”
Autophagy during viral infection — a double-edged sword (2018, background): “The lipid kinase vPS34 creates phosphatidylinositol-3-phosphate (PtdIns3P)-rich regions on the surface of donor membranes, including the endoplasmic reticulum (eR), Golgi apparatus, eR-mitochondria contact sites, endosomes and the plasma membrane [154] [155] [156] [157] [158] .”
Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons (2012, background): “Possible sources include endocytosed plasma membrane, ER, mitochondria, or Golgi membranes (Hollenbeck, 1993; Hayashi-Nishino et al., 2009; Hailey et al., 2010; Ravikumar et al., 2010; van der Vaart and Reggiori, 2010; Yen et al., 2010).”
Autophagy and apoptosis dysfunction in neurodegenerative disorders. (2014, neutral): “During further elongation and autophagosome formation around the selected cargo for degradation, recruitment of the membrane from endoplasmic reticulum, mitochondria and at times even nuclear membrane is well documented (Axe et al., 2008; Hailey et al., 2010).”
Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. (2010, background): “First, MFN-2 connects mitochondria with the endoplasmic reticulum (55), Figure 5.”
Mechanisms of mitophagy (2011, background): “Furthermore, recent reports indicate that, in some forms of autophagy, lipid for the autophagosomal membrane can be contributed by the ER (through contact with mitochondria, from which the autophagosomal membranes bu”