Mitochondrial presequence import: Multiple regulatory knobs fine-tune mitochondrial biogenesis and homeostasis

Biochimica Et Biophysica Acta. Molecular Cell Research
Cyril MoulinRaffaele Ieva

Abstract

Mitochondria are pivotal organelles for cellular signaling and metabolism, and their dysfunction leads to severe cellular stress. About 60-70% of the mitochondrial proteome consists of preproteins synthesized in the cytosol with an amino-terminal cleavable presequence targeting signal. The TIM23 complex transports presequence signals towards the mitochondrial matrix. Ultimately, the mature protein segments are either transported into the matrix or sorted to the inner membrane. To ensure accurate preprotein import into distinct mitochondrial sub-compartments, the TIM23 machinery adopts specific functional conformations and interacts with different partner complexes. Regulatory subunits modulate the translocase dynamics, tailoring the import reaction to the incoming preprotein. The mitochondrial membrane potential and the ATP generated via oxidative phosphorylation are key energy sources in driving the presequence import pathway. Thus, mitochondrial dysfunctions have rapid repercussions on biogenesis. Cellular mechanisms exploit the presequence import pathway to monitor mitochondrial dysfunctions and mount transcriptional and proteostatic responses to restore functionality.

Citations

Aug 19, 2020·Cell Research·Kuanxing GaoXiaorong Zhang
Jul 11, 2020·Biomolecules·Patrick HortenHeike Rampelt
Apr 13, 2020·Journal of Cellular and Molecular Medicine·Lucia-Doina Popov
Nov 2, 2019·Mitochondrion·Carmela Vazquez-CalvoMartin Ott
Apr 20, 2021·Biology of the Cell·Sebabrata Maity, Oishee Chakrabarti
Aug 3, 2021·Oxidative Medicine and Cellular Longevity·Leila ChodariAziz Eftekhari
Sep 7, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Tongyu C WikramanayakeRalf Paus

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