One-amino-acid trimming stabilizes mitochondrial protein complexes
A study shows that the mitochondrial intermediate peptidase ICP55 removes a single amino acid to create a stabilizing N-terminus; loss of ICP55 in human cells destabilizes hundreds of mitochondrial proteins, shifting them toward smaller subcomplexes and broadly disrupting mitochondrial complexes. Using global N-terminomics and complexome profiling, the researchers mapped ICP55 substrates, identified new cleavage motifs, and demonstrated that restoring ICP55 rescues complex integrity, revealing N-terminal proteoform control as a crucial layer of mitochondrial proteostasis with implications for disease.
