Selective Mechanisms Governing the Quality of Mitochondrially-Encoded Proteins
Description: Ensuring accurate synthesis and folding of newly produced proteins presents a critical challenge to cellular proteostasis. Well-studied protein quality control (PQC) systems associated with cytosolic ribosomes are in place to orchestrate the fate of nascent proteins. While we recently identified the first analogous system at mitochondrial ribosomes, the molecular mechanisms of the PQC of nascent mitochondrially-encoded proteins remain elusive.Building upon our preliminary results, we hypothesize that multiple PQC systems exist to oversee the proper production of mitochondrially-encoded proteins. Moreover, we propose that these systems exhibit substrate specificity, suggesting a dedicated role for each system in monitoring specific mitochondrially-encoded proteins.Combining sophisticated whole genome screens and cutting-edge biochemical methods, we aim to uncover novel PQC systems responsible for mitochondrially-encoded proteins and delineate the kinetics by which these systems recognize and sort specific nascent proteins. Further, we will assess the impact of these systems on cellular fitness during ageing and proteotoxic stress, validating whether activation of identified PQC systems can prolong cellular lifespan.Our project will elucidate fundamental biological mechanisms governing the PQC of mitochondrially-encoded proteins, laying the groundwork for developing future therapeutic interventions against age-related cellular decline.
Funder: Vetenskapsrådet
Amount: SEK 4,800,000
Funding type: fellowship
Funder scheme: Grant for positions or stipends
Start date: 2026-01-01
End date: 2029-12-31
Investigator: Andreas Kohler
Institution: Umeå University
Funded outputs count: 1
Funder award ID: 2025-05122
OpenAlex ID: G3607161598