Mitochondrial movement and distribution are fundamental to their function. Here we report a mechanism that regulates mitochondrial movement by anchoring mitochondria to the F-actin cytoskeleton. This mechanism is activated by an increase in glucose influx and the consequent O-GlcNAcylation of TRAK (Milton), a component of the mitochondrial motor-adaptor complex. The protein four and a half LIM domains protein 2 (FHL2) serves as the anchor. FHL2 associates with O-GlcNAcylated TRAK and is both necessary and sufficient to drive the accumulation of F-actin around mitochondria and to arrest mitochondrial movement by anchoring to F-actin. Disruption of F-actin restores mitochondrial movement that had been arrested by either TRAK O-GlcNAcylation or forced direction of FHL2 to mitochondria. This pathway for mitochondrial immobilization is present in both neurons and non-neuronal cells and can thereby adapt mitochondrial dynamics to changes in glucose availability.
FHL2 anchors mitochondria to actin and adapts mitochondrial dynamics to glucose supply
G. Pekkurnaz’s present address is Division of Biological Sciences, Neurobiology Section, University of California, San Diego, San Diego, CA.
W. Wei’s present address is Department of Biology, Stanford University, Palo Alto, CA.
- Award Id(s): NS072030
- Award Id(s): U54 HD090255
- Award Id(s): R01 GM11200
- Award Id(s): R01 GM069808
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Himanish Basu, Gulcin Pekkurnaz, Jill Falk, Wei Wei, Morven Chin, Judith Steen, Thomas L. Schwarz; FHL2 anchors mitochondria to actin and adapts mitochondrial dynamics to glucose supply. J Cell Biol 4 October 2021; 220 (10): e201912077. doi: https://doi.org/10.1083/jcb.201912077
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