Involvement of mitochondrial dynamics in the segregation of mitochondrial matrix proteins during stationary phase mitophagy.
Mitophagy, the autophagic degradation of mitochondria, is an important housekeeping function in eukaryotic cells, and defects in mitophagy correlate with ageing phenomena and with several neurodegenerative disorders. A central mechanistic question regarding mitophagy is whether mitochondria are consumed en masse, or whether an active process segregates defective molecules from functional ones within the mitochondrial network, thus allowing a more efficient culling mechanism. Here we combine a proteomic study with a molecular genetics and cell biology approach to determine whether such a segregation process occurs in yeast mitochondria. We find that different mitochondrial matrix proteins undergo mitophagic degradation at distinctly different rates, supporting the active segregation hypothesis. These differential degradation rates depend on mitochondrial dynamics, suggesting a mechanism coupling weak physical segregation with mitochondrial dynamics to achieve a distillation-like effect. In agreement, the rates of mitophagic degradation strongly correlate with the degree of physical segregation of specific matrix proteins.
1] The Institute for Biochemistry, Food Science, and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, P.O. Box 12, Rehovot, Israel 76100 [2] Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Porter Neuroscience Research Center Building 35, Room 2C-917 35 Convent Drive, Bethesda, Maryland 20892-3704, USA.
Hagai
H
Abeliovich
Mostafa
M
Zarei
Kristoffer T G
KT
Rigbolt
Richard J
RJ
Youle
Joern
J
Dengjel
D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism*; D063306:Mitophagy; D040901:Proteomics; D012568:Schizosaccharomyces
D024101:Mitochondrial Proteins