Mitochondria supply membranes for autophagosome biogenesis during starvation.
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.
Hailey
Dale W
DW
The Eunice Kennedy Shriver National Institutes of Child Health and Human Development, 18 Library Drive, Bethesda, MD 20892, USA.
Rambold
Angelika S
AS
Satpute-Krishnan
Prasanna
P
Mitra
Kasturi
K
Sougrat
Rachid
R
Kim
Peter K
PK
Lippincott-Schwartz
Jennifer
J
D000818:Animals; D002460:Cell Line; D002468:Cell Physiological Phenomena; D003470:Culture Media; D020558:GTP Phosphohydrolases; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism*; D051381:Rats
D003470:Culture Media; C503403:Fis1 protein, rat; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat