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Endoplasmic reticulum-associated mitochondria–cortex tether functions in the distribution and inheritance of mitochondria

Author:
Lackner, Laura L., Ping, Holly, Graef, Martin, Murley, Andrew, Nunnari, Jodi
Source:
Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.6 pp. E458
ISSN:
0027-8424
Subject:
cortex, endoplasmic reticulum, genes, mitochondria, proteins, viability
Abstract:
To elucidate the functional roles of mitochondrial dynamics in vivo, we identified genes that become essential in cells lacking the dynamin-related proteins Fzo1 and Dnm1, which are required for mitochondrial fusion and division, respectively. The screen identified Num1, a cortical protein implicated in mitochondrial division and distribution that also functions in nuclear migration. Our data indicate that Num1, together with Mdm36, forms a physical tether that robustly anchors mitochondria to the cell cortex but plays no direct role in mitochondrial division. Our analysis indicates that Num1-dependent anchoring is essential for distribution of the static mitochondrial network in fzo1 dnm1 cells. Consistently, expression of a synthetic mitochondria–cortex tether rescues the viability of fzo1 dnm1 num1 cells. We find that the cortical endoplasmic reticulum (ER) also is a constituent of the Num1 mitochondria–cortex tether, suggesting an active role for the ER in mitochondrial positioning in cells. Thus, taken together, our findings identify Num1 as a key component of a mitochondria–ER–cortex anchor, which we termed “MECA,” that functions in parallel with mitochondrial dynamics to distribute and position the essential mitochondrial network.
Agid:
1785066