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

Laura L. Lackner*, Holly Ping, Martin Graef, Andrew Murley, Jodi Nunnari

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)E458-E467
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number6
DOIs
StatePublished - Feb 5 2013

ASJC Scopus subject areas

  • General

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