Outer mitochondrial membrane E3 Ub ligase MARCH5 controls de novo peroxisome biogenesis.

Autor:	Verhoeven N; Center for Biomedical Engineering and Technology, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Biochemistry and Molecular Biology, University Hospital Basel, University of Basel, Basel, Switzerland., Oshima Y; Center for Biomedical Engineering and Technology, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Biochemistry and Molecular Biology, University Hospital Basel, University of Basel, Basel, Switzerland., Cartier E; Center for Biomedical Engineering and Technology, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Biochemistry and Molecular Biology, University Hospital Basel, University of Basel, Basel, Switzerland., Bippes CC; Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland., Neutzner A; Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland., Boyman L; Center for Biomedical Engineering and Technology, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Karbowski M; Center for Biomedical Engineering and Technology, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Biochemistry and Molecular Biology, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: mkarbowski@som.umaryland.edu.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2024 Oct 15. Date of Electronic Publication: 2024 Oct 15.
DOI:	10.1016/j.devcel.2024.09.010
Abstrakt:	We report that the outer mitochondrial membrane (OMM)-associated E3 Ub ligase MARCH5 is vital for generating mitochondria-derived pre-peroxisomes. In human immortalized cells, MARCH5 knockout leads to the accumulation of immature peroxisomes, reduced fatty-acid-induced peroxisomal biogenesis, and abnormal peroxisome biogenesis in MARCH5/Pex14 and MARCH5/Pex3 dko cells. Upon fatty-acid-induced peroxisomal biogenesis, MARCH5 redistributes to peroxisomes, and ubiquitination activity-deficient mutants of MARCH5 accumulate on peroxisomes containing high levels of the OMM protein Tom20 (mitochondria-derived pre-peroxisomes). Similarly, depletion of peroxisome biogenesis factor Pex14 leads to the accumulation of MARCH5- and Tom20-positive pre-peroxisomes, whereas no peroxisomes are detected in MARCH5/Pex14 dko cells. Inconsistent with MARCH5 merely acting as a quality factor, mitochondrial decline is not evident in tested models. Furthermore, reduced expression of peroxisomal proteins is detected in MARCH5 -/- cells, whereas some of these proteins are stabilized in peroxisome biogenesis deficiency models lacking MARCH5 expression. Thus, MARCH5 is central for mitochondria-dependent peroxisome biogenesis. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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