دورية أكاديمية
أعرض في EDS

An Inner Mitochondrial Membrane Microprotein from the SLC35A4 Upstream ORF Regulates Cellular Metabolism.

التفاصيل البيبلوغرافية
العنوان: An Inner Mitochondrial Membrane Microprotein from the SLC35A4 Upstream ORF Regulates Cellular Metabolism.
المؤلفون: Rocha AL; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA., Pai V; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA., Perkins G; National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA., Chang T; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA., Ma J; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA., De Souza EV; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA., Chu Q; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA., Vaughan JM; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA., Diedrich JK; Mass Spectrometry Core for Proteomics and Metabolomics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, USA., Ellisman MH; National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA. Electronic address: mellisman@ucsd.edu., Saghatelian A; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA, USA. Electronic address: asaghatelian@salk.edu.
المصدر: Journal of molecular biology [J Mol Biol] 2024 May 15; Vol. 436 (10), pp. 168559. Date of Electronic Publication: 2024 Apr 03.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 2985088R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1089-8638 (Electronic) Linking ISSN: 00222836 NLM ISO Abbreviation: J Mol Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: 1959- : London : Academic Press
مواضيع طبية MeSH: Mitochondrial Membranes*/metabolism , Mitochondrial Proteins*/metabolism , Mitochondrial Proteins*/genetics , Open Reading Frames*/genetics , Nucleotide Transport Proteins*/genetics , Nucleotide Transport Proteins*/metabolism, Humans ; 5' Untranslated Regions/genetics ; Amino Acid Sequence ; Mitochondria/metabolism ; Mitochondria/genetics ; Protein Biosynthesis ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; HEK293 Cells
مستخلص: Upstream open reading frames (uORFs) are cis-acting elements that can dynamically regulate the translation of downstream ORFs by suppressing downstream translation under basal conditions and, in some cases, increasing downstream translation under stress conditions. Computational and empirical methods have identified uORFs in the 5'-UTRs of approximately half of all mouse and human transcripts, making uORFs one of the largest regulatory elements known. Because the prevailing dogma was that eukaryotic mRNAs produce a single functional protein, the peptides and small proteins, or microproteins, encoded by uORFs were rarely studied. We hypothesized that a uORF in the SLC35A4 mRNA is producing a functional microprotein (SLC35A4-MP) because of its conserved amino acid sequence. Through a series of biochemical and cellular experiments, we find that the 103-amino acid SLC35A4-MP is a single-pass transmembrane inner mitochondrial membrane (IMM) microprotein. The IMM contains the protein machinery crucial for cellular respiration and ATP generation, and loss of function studies with SLC35A4-MP significantly diminish maximal cellular respiration, indicating a vital role for this microprotein in cellular metabolism. The findings add SLC35A4-MP to the growing list of functional microproteins and, more generally, indicate that uORFs that encode conserved microproteins are an untapped reservoir of functional microproteins.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
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معلومات مُعتمدة: R56 AG062479 United States AG NIA NIH HHS; RF1 MH129261 United States MH NIMH NIH HHS; R01 AG065549 United States AG NIA NIH HHS; S10 OD021784 United States OD NIH HHS; R01 GM138780 United States GM NIGMS NIH HHS; U24 NS120055 United States NS NINDS NIH HHS; R01 NS108934 United States NS NINDS NIH HHS; RF1 AG062479 United States AG NIA NIH HHS; R01 AG081037 United States AG NIA NIH HHS; R01 GM102491 United States GM NIGMS NIH HHS; P30 CA014195 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: cellular metabolism; inner mitochondrial membrane; microprotein; mitochondria; upstream open reading frame (uORF)
المشرفين على المادة: 0 (5' Untranslated Regions)
0 (Mitochondrial Proteins)
0 (RNA, Messenger)
0 (SLC35A4 protein, human)
0 (Nucleotide Transport Proteins)
تواريخ الأحداث: Date Created: 20240405 Date Completed: 20240512 Latest Revision: 20240803
رمز التحديث: 20240803
مُعرف محوري في PubMed: PMC11292582
DOI: 10.1016/j.jmb.2024.168559
PMID: 38580077
قاعدة البيانات: MEDLINE
الوصف
تدمد:1089-8638
DOI:10.1016/j.jmb.2024.168559