Patron, Maria, Tarasenko, Daryna, Nolte, Hendrik, Kroczek, Lara ORCID: 0000-0001-7462-6768, Ghosh, Mausumi, Ohba, Yohsuke, Lasarzewski, Yvonne, Ahmadi, Zeinab Alsadat, Cabrera-Orefice, Alfredo ORCID: 0000-0002-2042-3794, Eyiama, Akinori, Kellermann, Tim, Rugarli, Elena, I, Brandt, Ulrich ORCID: 0000-0003-1869-6811, Meinecke, Michael ORCID: 0000-0003-1414-6951 and Langer, Thomas (2022). Regulation of mitochondrial proteostasis by the proton gradient. Embo J., 41 (16). HOBOKEN: WILEY. ISSN 1460-2075

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Abstract

Mitochondria adapt to different energetic demands reshaping their proteome. Mitochondrial proteases are emerging as key regulators of these adaptive processes. Here, we use a multiproteomic approach to demonstrate the regulation of the m-AAA protease AFG3L2 by the mitochondrial proton gradient, coupling mitochondrial protein turnover to the energetic status of mitochondria. We identify TMBIM5 (previously also known as GHITM or MICS1) as a Ca2+/H+ exchanger in the mitochondrial inner membrane, which binds to and inhibits the m-AAA protease. TMBIM5 ensures cell survival and respiration, allowing Ca2+ efflux from mitochondria and limiting mitochondrial hyperpolarization. Persistent hyperpolarization, however, triggers degradation of TMBIM5 and activation of the m-AAA protease. The m-AAA protease broadly remodels the mitochondrial proteome and mediates the proteolytic breakdown of respiratory complex I to confine ROS production and oxidative damage in hyperpolarized mitochondria. TMBIM5 thus integrates mitochondrial Ca2+ signaling and the energetic status of mitochondria with protein turnover rates to reshape the mitochondrial proteome and adjust the cellular metabolism.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Patron, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tarasenko, DarynaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nolte, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kroczek, LaraUNSPECIFIEDorcid.org/0000-0001-7462-6768UNSPECIFIED
Ghosh, MausumiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ohba, YohsukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lasarzewski, YvonneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahmadi, Zeinab AlsadatUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cabrera-Orefice, AlfredoUNSPECIFIEDorcid.org/0000-0002-2042-3794UNSPECIFIED
Eyiama, AkinoriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kellermann, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rugarli, Elena, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brandt, UlrichUNSPECIFIEDorcid.org/0000-0003-1869-6811UNSPECIFIED
Meinecke, MichaelUNSPECIFIEDorcid.org/0000-0003-1414-6951UNSPECIFIED
Langer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-682763
DOI: 10.15252/embj.2021110476
Journal or Publication Title: Embo J.
Volume: 41
Number: 16
Date: 2022
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1460-2075
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
M-AAA PROTEASE; CHAPERONE-LIKE ACTIVITY; COMPLEX-I; SPASTIC PARAPLEGIA; MUTATIONS; IDENTIFICATION; MEMBRANE; CHANNEL; HOMEOSTASIS; COMPONENTMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/68276

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