Distinct roles of the two isoforms of the dynamin-like GTPase Mgm1 in mitochondrial fusion

Abstract 

The mitochondrial dynamin-like GTPase Mgm1 exists as a long (l-Mgm1) and a short isoform (s-Mgm1). They both are essential for mitochondrial fusion. Here we show that the isoforms interact in a homotypic and heterotypic manner. Their submitochondrial distribution between inner boundary membrane and cristae was markedly different. Overexpression of l-Mgm1 exerts a dominant negative effect on mitochondrial fusion. A functional GTPase domain is required only in s-Mgm1 but not in l-Mgm1. We propose that l-Mgm1 acts primarily as an anchor in the inner membrane that in concert with the GTPase activity of s-Mgm1 mediates the fusion of inner membranes.

Abbreviations: TM, transmembrane segment of Mgm1, RCR, rhomboid cleavage region, IBM, mitochondrial inner boundary membrane, OM, mitochondrial outer membrane, CM, crista membrane, s-Mgm1, short isoform of Mgm1, l-Mgm1, long isoform of Mgm1, 5-FOA, 5-fluorouracil-6-carboxylic acid monohydrate, mtDNA, mitochondrial DNA

Keywords: Mitochondria, Membrane fusion, Mitochondrial DNA, Mgm1, Genetic analysis, Dynamin-like GTPase