biostudies-literatureBons JAgence Nationale de la Recherche (ANR)1085-1095https://www.ebi.ac.uk/biostudies/studies/S-EPMC6553941biostudies-literatureUnknown18(6)All but thirteen mammalian mitochondrial proteins are encoded by the nuclear genome, translated in the cytosol and then imported into the mitochondria. For a significant proportion of the mitochondrial proteins, import is coupled with the cleavage of a presequence called the transit peptide, and the formation of a new N-terminus. Determination of the neo N-termini has been investigated by proteomic approaches in several systems, but generally in a static way to compile as many N-termini as possible. In the present study, we have investigated how the mitochondrial proteome and N-terminome react to chemical stimuli that alter mitochondrial metabolism, namely zinc ions and rapamycin. To this end, we have used a strategy that analyzes both internal and N-terminal peptides in a single run, the Molecular & cellular proteomics : MCPA Combined N-terminomics and Shotgun Proteomics Approach to Investigate the Responses of Human Cells to Rapamycin and Zinc at the Mitochondrial Level.PMC6553941energiomeCarapito CBons JMacron CRompais MAude-Garcia CCianferani SVaca-Jacome SARabilloud TfalseA Combined N-terminomics and Shotgun Proteomics Approach to Investigate the Responses of Human Cells to Rapamycin and Zinc at the Mitochondrial Level.All but thirteen mammalian mitochondrial proteins are encoded by the nuclear genome, translated in the cytosol and then imported into the mitochondria. For a significant proportion of the mitochondrial proteins, import is coupled with the cleavage of a presequence called the transit peptide, and the formation of a new N-terminus. Determination of the neo N-termini has been investigated by proteomic approaches in several systems, but generally in a static way to compile as many N-termini as possible. In the present study, we have investigated how the mitochondrial proteome and N-terminome react to chemical stimuli that alter mitochondrial metabolism, namely zinc ions and rapamycin. To this end, we have used a strategy that analyzes both internal and N-terminal peptides in a single run, the 2019-01-01T00:00:00Z2019 Jun2026-04-07T17:07:04.471Z2020-06-04T07:07:49ZS-EPMC65539413115443710.1074/mcp.ra118.00126910.1074/mcp.RA118.001269