3.A.32.  The Mitochondrial Outer Membrane-associated Protein Degradation (MOM-PD) Family

Maintaining the essential functions of mitochondria requires mechanisms to recognize and remove misfolded proteins (quality control pathways for misfolded mitochondrial proteins). Metzger et al. 2020 establish temperature-sensitive (ts-) peripheral mitochondrial outer membrane (MOM) proteins as novel model QC substrates in Saccharomyces cerevisiae. The ts- proteins sen2-1HA(ts) and sam35-2HA(ts) are degraded from the MOM by the ubiquitin-proteasome system. Ubiquitination of sen2-1HA(ts) is mediated by the ubiquitin ligase (E3) Ubr1, while sam35-2HA(ts) is ubiquitinated primarily by San1. Mitochondria-associated degradation (MAD) of both substrates requires the SSA family of Hsp70s and the Hsp40 Sis1, providing evidence for chaperone involvement in MAD. In addition to a role for the Cdc48-Npl4-Ufd1 AAA-ATPase complex, Doa1 and a mitochondrial pool of the transmembrane Cdc48 adaptor, Ubx2, are implicated in their degradation. Thus, a unique QC pathway comprised of a combination of cytosolic and mitochondrial factors distinguishes it from other cellular QC pathways (Metzger et al. 2020).


 

References:

Metzger, M.B., J.L. Scales, M.F. Dunklebarger, J. Loncarek, and A.M. Weissman. (2020). A protein quality control pathway at the mitochondrial outer membrane. Elife 9:.