3.A.16.1.6
The yeast multicomponent mitochondrial outer membrane-associated protein degradation (MOM-PD) pathway. Maintaining the essential functions of mitochondria requires mechanisms to recognize and remove misfolded proteins (quality control pathways). Metzger et al. 2020 established temperature-sensitive (ts-) peripheral mitochondrial outer membrane (MOM) proteins as novel model QC substrates in Saccharomyces cerevisiae. The ts-proteins Sen2-1HA(ts) (P16658; 329 aas, 0 TMSs) and Sam35-2HA(ts) (P14693; 329 aas and 1 TMS) are degraded using the MOM-PD pathway involving 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 (e.g., P10591; 642 aas and 0 TMSs) and the Hsp40 Sis1 (P25294; 352 aas and 0 TMSs), providing evidence for chaperone involvement in MOM-PD. In addition to a role for the Cdc48-Npl4-Ufd1 AAA-ATPase complex (see TC# 3.A.16.1.2), Doa1 and a mitochondrial pool of the transmembrane Cdc48 adaptor, Ubx2, are implicated in their degradation. Thus, a unique QC pathway consists of a combination of cytosolic and mitochondrial factors and distinguishes it from other cellular QC pathways (Metzger et al. 2020). Nevertheless, most of the protein constituents have homologs in TC family 3.A.16.