Finger, Yannik, Habich, Markus, Gerlich, Sarah, Urbanczyk, Sophia, van de Logt, Erik, Koch, Julian ORCID: 0000-0001-7829-3411, Schu, Laura, Lapacz, Kim Jasmin, Ali, Muna, Petrungaro, Carmelina, Salscheider, Silja Lucia, Pichlo, Christian, Baumann, Ulrich, Mielenz, Dirk, Dengjel, Joern, Brachvogel, Bent, Hofmann, Kay and Riemer, Jan (2020). Proteasomal degradation induced by DPP9-mediated processing competes with mitochondrial protein import. Embo J., 39 (19). HOBOKEN: WILEY. ISSN 1460-2075

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Finger, YannikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Habich, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerlich, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Urbanczyk, SophiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van de Logt, ErikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, JulianUNSPECIFIEDorcid.org/0000-0001-7829-3411UNSPECIFIED
Schu, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lapacz, Kim JasminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ali, MunaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petrungaro, CarmelinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salscheider, Silja LuciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pichlo, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baumann, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mielenz, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dengjel, JoernUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brachvogel, BentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofmann, KayUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riemer, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-317087
Journal or Publication Title: Embo J.
Volume: 39
Number: 19
Date: 2020
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1460-2075
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ADENYLATE KINASE 2; MULTIPLE SEQUENCE ALIGNMENT; DIPEPTIDYL PEPTIDASES 8; INTERMEMBRANE SPACE; SUBSTRATE-INHIBITION; CELLULAR HOMEOSTASIS; ENERGY-METABOLISM; DISULFIDE BONDS; IDENTIFICATION; COMPLEXMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31708

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