Starvation-induced autophagosomes engulf cytosol and/or organelles and deliver them
to lysosomes for degradation, thereby resupplying 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, the outer membrane of
mitochondria participates in autophagosome biogenesis. The early autophagosomal marker,
Atg5, transiently localizes to punctae on mitochondria, followed by the late autophagosomal
marker, LC3. The tail-anchor of an outer mitochondrial membrane protein also labels
autophagosomes and is sufficient to deliver another outer mitochondrial membrane protein,
Fis1, to autophagosomes. The fluorescent lipid NBD-PS (converted to NBD-phosphotidylethanolamine
in mitochondria) transfers from mitochondria to autophagosomes. Photobleaching reveals
membranes of mitochondria and autophagosomes are transiently shared. Disruption of
mitochondria/ER connections by mitofusin2 depletion dramatically impairs starvation-induced
autophagy. Mitochondria thus play a central role in starvation-induced autophagy,
contributing membrane to autophagosomes.
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