FHL2 anchors mitochondria to actin and adapts mitochondrial dynamics to glucose supply

2021/08/03 by Himanish Basu, Gülçin Pekkurnaz, Gulcin Pekkurnaz +7 · 25 citations
Biochemistry, Genetics and Molecular Biology · #Mitochondrial Function and Pathology #ATP Synthase and ATPases Research #Metabolism and Genetic Disorders

paper · doi:10.1083/jcb.201912077

Abstract

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.

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