MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission.
The modification of proteins by the small ubiquitin-like modifier (SUMO) is known to regulate an increasing array of cellular processes. SUMOylation of the mitochondrial fission GTPase dynamin-related protein 1 (DRP1) stimulates mitochondrial fission, suggesting that SUMOylation has an important function in mitochondrial dynamics. The conjugation of SUMO to its substrates requires a regulatory SUMO E3 ligase; however, so far, none has been functionally associated with the mitochondria. By using biochemical assays, overexpression and RNA interference experiments, we characterized the mitochondrial-anchored protein ligase (MAPL) as the first mitochondrial-anchored SUMO E3 ligase. Furthermore, we show that DRP1 is a substrate for MAPL, providing a direct link between MAPL and the fission machinery. Importantly, the large number of unidentified mitochondrial SUMO targets suggests a global role for SUMOylation in mitochondrial function, placing MAPL as a crucial component in the regulation of multiple conjugation events.
Braschi
Emélie
E
University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Zunino
Rodolfo
R
McBride
Heidi M
HM
D000818:Animals; D002417:Cattle; D034281:Dynamins / Q000378:metabolism; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000201:enzymology* / Q000502:physiology* / Q000648:ultrastructure; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; C529067:MUL1 protein, human; D044767:Ubiquitin-Protein Ligases; D034281:Dynamins