Proteasomal degradation induced by DPP9-mediated processing competes with mitochondrial protein import

Finger, Yannik; Habich, Markus; Gerlich, Sarah; Urbanczyk, Sophia; Logt, Erik; Koch, Julian; Schu, Laura; Lapacz, Kim Jasmin; Ali, Muna; Petrungaro, Carmelina; Salscheider, Silja Lucia; Pichlo, Christian; Baumann, Ulrich; Mielenz, Dirk; Dengjel, Jörn; Brachvogel, Bent; Hofmann, Kay; Riemer, Jan

doi:10.15252/embj.2019103889

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Proteasomal degradation induced by DPP9-mediated processing competes with mitochondrial protein import

Finger, Yannik Institute of Biochemistry Redox Biochemistry University of Cologne Cologne Germany
Habich, Markus Institute of Biochemistry Redox Biochemistry University of Cologne Cologne Germany
Gerlich, Sarah Institute of Biochemistry Redox Biochemistry University of Cologne Cologne Germany
Urbanczyk, Sophia Division of Molecular Immunology Department of Internal Medicine III Nikolaus‐Fiebiger‐Center University of Erlangen‐Nürnberg Erlangen Germany
Logt, Erik Institute of Biochemistry Redox Biochemistry University of Cologne Cologne Germany
Koch, Julian Institute of Biochemistry Redox Biochemistry University of Cologne Cologne Germany
Schu, Laura Institute of Biochemistry Redox Biochemistry University of Cologne Cologne Germany
Lapacz, Kim Jasmin Institute of Biochemistry Redox Biochemistry University of Cologne Cologne Germany
Ali, Muna Institute of Biochemistry Redox Biochemistry University of Cologne Cologne Germany
Petrungaro, Carmelina Institute of Biochemistry Redox Biochemistry University of Cologne Cologne Germany
Salscheider, Silja Lucia Institute of Biochemistry Redox Biochemistry University of Cologne Cologne Germany
Pichlo, Christian Institute of Biochemistry University of Cologne Cologne Germany
Baumann, Ulrich Institute of Biochemistry University of Cologne Cologne Germany
Mielenz, Dirk Division of Molecular Immunology Department of Internal Medicine III Nikolaus‐Fiebiger‐Center University of Erlangen‐Nürnberg Erlangen Germany
Dengjel, Jörn Department of Biology University of Fribourg Fribourg Switzerland
Brachvogel, Bent Department of Pediatrics and Adolescent Medicine Experimental Neonatology Faculty of Medicine University of Cologne Cologne Germany - Center for Biochemistry Faculty of Medicine University of Cologne Cologne Germany
Hofmann, Kay Institute of Genetics University of Cologne Cologne Germany
Riemer, Jan Institute of Biochemistry Redox Biochemistry University of Cologne Cologne Germany - Cologne Excellence Cluster on Cellular Stress Responses in Aging‐Associated Diseases (CECAD) University of Cologne Cologne Germany

20.08.2020

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The EMBO Journal. - 2020, vol. 39, no. 19, p. e103889

English Plasticity of the proteome is critical to adapt to varying conditions. Control of mitochondrial protein import contributes to this plasticity. Here, we identified a pathway that regulates mitochondrial protein import by regulated N-terminal processing. We demonstrate that dipeptidyl peptidases 8/9 (DPP8/9) mediate the N-terminal processing of adenylate kinase 2 (AK2) en route to mitochondria. We show that AK2 is a substrate of the mitochondrial disulfide relay, thus lacking an N-terminal mitochondrial targeting sequence and undergoing comparatively slow import. DPP9- mediated processing of AK2 induces its rapid proteasomal degradation and prevents cytosolic accumulation of enzymatically active AK2. Besides AK2, we identify more than 100 mitochondrial proteins with putative DPP8/9 recognition sites and demonstrate that DPP8/9 influence the cellular levels of a number of these proteins. Collectively, we provide in this study a conceptual framework on how regulated cytosolic processing controls levels of mitochondrial proteins as well as their dual localization to mitochondria and other compartments.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

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