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Two domains of Tim50 coordinate translocation of proteins across the two mitochondrial membranes

Hundreds of mitochondrial proteins with N-terminal presequences are translocated across the outer and inner mitochondrial membranes via the TOM and TIM23 complexes, respectively. How translocation of proteins across two mitochondrial membranes is coordinated is largely unknown. Here, we show that th...

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Autores principales: Genge, Marcel G, Roy Chowdhury, Shalini, Dohnálek, Vít, Yunoki, Kaori, Hirashima, Takashi, Endo, Toshiya, Doležal, Pavel, Mokranjac, Dejana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520260/
https://www.ncbi.nlm.nih.gov/pubmed/37748811
http://dx.doi.org/10.26508/lsa.202302122
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author Genge, Marcel G
Roy Chowdhury, Shalini
Dohnálek, Vít
Yunoki, Kaori
Hirashima, Takashi
Endo, Toshiya
Doležal, Pavel
Mokranjac, Dejana
author_facet Genge, Marcel G
Roy Chowdhury, Shalini
Dohnálek, Vít
Yunoki, Kaori
Hirashima, Takashi
Endo, Toshiya
Doležal, Pavel
Mokranjac, Dejana
author_sort Genge, Marcel G
collection PubMed
description Hundreds of mitochondrial proteins with N-terminal presequences are translocated across the outer and inner mitochondrial membranes via the TOM and TIM23 complexes, respectively. How translocation of proteins across two mitochondrial membranes is coordinated is largely unknown. Here, we show that the two domains of Tim50 in the intermembrane space, named core and PBD, both have essential roles in this process. Building upon the surprising observation that the two domains of Tim50 can complement each other in trans, we establish that the core domain contains the main presequence-binding site and serves as the main recruitment point to the TIM23 complex. On the other hand, the PBD plays, directly or indirectly, a critical role in cooperation of the TOM and TIM23 complexes and supports the receptor function of Tim50. Thus, the two domains of Tim50 both have essential but distinct roles and together coordinate translocation of proteins across two mitochondrial membranes.
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spelling pubmed-105202602023-09-27 Two domains of Tim50 coordinate translocation of proteins across the two mitochondrial membranes Genge, Marcel G Roy Chowdhury, Shalini Dohnálek, Vít Yunoki, Kaori Hirashima, Takashi Endo, Toshiya Doležal, Pavel Mokranjac, Dejana Life Sci Alliance Research Articles Hundreds of mitochondrial proteins with N-terminal presequences are translocated across the outer and inner mitochondrial membranes via the TOM and TIM23 complexes, respectively. How translocation of proteins across two mitochondrial membranes is coordinated is largely unknown. Here, we show that the two domains of Tim50 in the intermembrane space, named core and PBD, both have essential roles in this process. Building upon the surprising observation that the two domains of Tim50 can complement each other in trans, we establish that the core domain contains the main presequence-binding site and serves as the main recruitment point to the TIM23 complex. On the other hand, the PBD plays, directly or indirectly, a critical role in cooperation of the TOM and TIM23 complexes and supports the receptor function of Tim50. Thus, the two domains of Tim50 both have essential but distinct roles and together coordinate translocation of proteins across two mitochondrial membranes. Life Science Alliance LLC 2023-09-25 /pmc/articles/PMC10520260/ /pubmed/37748811 http://dx.doi.org/10.26508/lsa.202302122 Text en © 2023 Genge et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Genge, Marcel G
Roy Chowdhury, Shalini
Dohnálek, Vít
Yunoki, Kaori
Hirashima, Takashi
Endo, Toshiya
Doležal, Pavel
Mokranjac, Dejana
Two domains of Tim50 coordinate translocation of proteins across the two mitochondrial membranes
title Two domains of Tim50 coordinate translocation of proteins across the two mitochondrial membranes
title_full Two domains of Tim50 coordinate translocation of proteins across the two mitochondrial membranes
title_fullStr Two domains of Tim50 coordinate translocation of proteins across the two mitochondrial membranes
title_full_unstemmed Two domains of Tim50 coordinate translocation of proteins across the two mitochondrial membranes
title_short Two domains of Tim50 coordinate translocation of proteins across the two mitochondrial membranes
title_sort two domains of tim50 coordinate translocation of proteins across the two mitochondrial membranes
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520260/
https://www.ncbi.nlm.nih.gov/pubmed/37748811
http://dx.doi.org/10.26508/lsa.202302122
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