Insights into protein removal from the trypanosome mitochondrium

Schematic model of the trypanosomal mitochondria-associated degradation (MAD) pathways triggered by the absence of pATOM36.

Cells need to be able to remove and degrade proteins which are no longer needed, the Schneider lab and collaborators could now obtain new insights how removal of proteins from the outer mitochondrial membrane of trypansomes work. Several proteins including two AAA-ATPases are involved in this process and they speculate that this quality control pathway might be conserved in yeast and humans, based on homologus proteins. Their findings have been published in the article "A Msp1-containing complex removes orphaned proteins in the mitochondrial outer membrane of T. brucei" in Life Science Alliance. 

The AAA-ATPase Msp1 extracts mislocalised outer membrane proteins and thus contributes to mitochondrial proteostasis. Using pulldown experiments, we show that trypanosomal Msp1 localises to both glycosomes and the mitochondrial outer membrane, where it forms a complex with four outer membrane proteins. The trypanosome-specific pATOM36 mediates complex assembly of a-helically anchored mitochondrial outer membrane proteins such as protein translocase subunits. Inhibition of their assembly triggers a pathway that results in the proteasomal digestion of unassembled substrates. Using inducible single, double, and triple RNAi cell lines combined with proteomic analyses, we demonstrate that not only Msp1 but also the trypanosomal homolog of the AAA-ATPase VCP are implicated in this quality control pathway. Moreover, in the absence of VCP three out of the four Msp1-interacting mitochondrial proteins are required for efficient proteasomal digestion of pATOM36 substrates, suggesting they act in concert with Msp1. pATOM36 is a functional analog of the yeast mitochondrial import complex complex and possibly of human mitochondrial animal-specific carrier homolog 2, suggesting that similar mitochondrial quality control pathways linked to Msp1 might also exist in yeast and humans.

Read the Publication in Life Science Alliance (Open Access)

Website Schneider Lab

Abstract, figure and title from Gerber et al (2023) Life Sci Alliance published under a CC BY 4.0 license.