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PXD030258

PXD030258 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMitochondrial microproteins link metabolic cues to respiratory chain biogenesis
DescriptionElectron transport chain (ETC) biogenesis is tightly coupled to energy levels and availability of ETC subunits. Coenzyme Q: cytochrome c oxidoreductase (complex III or CIII) occupies a central position in the ETC, receiving electrons from diverse fuel sources to control the ubiquinol:ubiquinone (CoQH2/CoQ) ratio. As such, CIII is an attractive node for controlling ETC biogenesis during metabolic stress. Here, we report the discovery of mammalian CoOrdinator of Mitochondrial CYTB or “COM” complexes that regulate CIII biogenesis in a step-wise fashion in response to nutrient and nuclear-encoded ETC subunit availability. The COMA complex, consisting of UQCC1/2 and the membrane anchor C16ORF91 (UQCC4), facilitates the translation of CIII enzymatic core subunit CYTB. Subsequently, microproteins SMIM4 and BRAWNIN, together with COMA subunits form the COMB complex that stabilizes nascent CYTB. Finally, UQCC3-containing COMC promotes CTYB maturation and association with downstream CIII subunits. This stepwise assembly enables cells to adapt to metabolic stress by increasing CIII biogenesis and inducing an integrated stress response when challenged. Furthermore, when nuclear CIII subunits are unavailable for assembly, COMB is required to chaperone nascent CYTB to prevent OXPHOS collapse. Our studies highlight CYTB synthesis as a key regulatory node of ETC biogenesis, and uncover the roles of mito-SEPs in mitochondrial homeostasis during energy stress.
HostingRepositoryPRIDE
AnnounceDate2022-09-26
AnnouncementXMLSubmission_2022-09-25_16:33:12.432.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDavid Stroud
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480; Q Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-12-08 12:39:45ID requested
12022-09-25 16:33:13announced
Publication List
Liang C, Zhang S, Robinson D, Ploeg MV, Wilson R, Nah J, Taylor D, Beh S, Lim R, Sun L, Muoio DM, Stroud DA, Ho L, Mitochondrial microproteins link metabolic cues to respiratory chain biogenesis. Cell Rep, 40(7):111204(2022) [pubmed]
Keyword List
submitter keyword: mitochondria, micropeptides, SEP, OXPHOS, metabolism
Contact List
David Stroud
contact affiliationDepartment of Biochemistry and Pharmacology, The Bio21 Molecular Science & Biotechnology Institute, University of Melbourne, 30 Flemington Rd, Parkville Victoria 3052, Australia
contact emaildavid.stroud@unimelb.edu.au
lab head
David Stroud
contact affiliationThe University of Melbourne
contact emaildavid.stroud@unimelb.edu.au
dataset submitter
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