Unclogging of the TOM complex under import stress

Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Abstract Mitochondrial functions and biogenesis depend on the import of more than 1,000 proteins which are synthesized as precursor cytosolic ribosomes. protein translocases sort into mitochondrial sub-compartments: outer inner membrane, intermembrane space matrix. The translocase membrane (TOM complex) constitutes major site for most these proteins. Defective translocases, premature folding precursor, or depletion potential can cause clogging TOM channel by a protein. This impairs further leads to accumulation in cell that perturbates homeostasis, leading proteotoxic stress cell. Therefore, unclogging translocon is critical maintaining cellular function. Ubiquitylation AAA-ATPases play central role extraction deliver them proteasome degradation. Here we summarize our understanding molecular mechanisms remove such translocation-stalled from translocation regenerate complex import.

Language: Английский

Alternative start codon selection shapes mitochondrial function during evolution, homeostasis, and disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Mitochondrial endosymbiosis was a pivotal event in eukaryotic evolution, requiring core proteins to adapt function both within the mitochondria and host cell. Here, we systematically profile localization of protein isoforms generated by alternate start codon selection during translation. We identify hundreds pairs differentially-localized isoforms, many which affect mitochondrial targeting are essential for function. The emergence dual-localized coincides with acquisition early evolution. further reveal that eukaryotes use diverse mechanisms-such as leaky ribosome scanning, alternative transcription, paralog duplication-to maintain production isoforms. Finally, multiple specifically dysregulated rare disease patient mutations demonstrate how these can help explain unique clinical presentations. Together, our findings illuminate evolutionary pathological relevance translation initiation, offering new insights into molecular underpinnings biology.

Language: Английский

Cell biology: Mitochondrial protease degrades unoccupied translocases upon import stress

Current Biology, Journal Year: 2025, Volume and Issue: 35(8), P. R287 - R290

Published: April 1, 2025

Language: Английский