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Mitochondrion. 2018 Mar;39:51-59. doi: 10.1016/j.mito.2017.08.013. Epub 2017 Sep 1.

Mitochondrial disruption in peroxisome deficient cells is hepatocyte selective but is not mediated by common hepatic peroxisomal metabolites.

Author information

1
KU Leuven - University of Leuven, Department of Pharmaceutical and Pharmacological Sciences, Laboratory of Cell Metabolism, B-3000 Leuven, Belgium.
2
Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
3
Department of Biochemistry, NCCR Chemical Biology, University of Geneva, 1211 Geneva, Switzerland.
4
Dept Basic Medical Sciences, UGhent, B-9000 Ghent, Belgium.
5
Neurolipid Biology group, Instituto de Biologia Molecular e Celular - IBMC, Instituto de Inovação e Investigação em Saúde, University of Porto, 4200-135 Porto, Portugal.
6
VIB-KU Leuven Centre for Cancer Biology, Laboratory of Angiogenesis and Vascular Metabolism, B-3000 Leuven, Belgium.
7
KU Leuven - University of Leuven, Department of Cellular and Molecular Medicine, Laboratory for Lipid Biochemistry and Protein Interactions, KU Leuven, B-3000 Leuven, Belgium. Electronic address: Paul.Vanveldhoven@kuleuven.be.
8
KU Leuven - University of Leuven, Department of Pharmaceutical and Pharmacological Sciences, Laboratory of Cell Metabolism, B-3000 Leuven, Belgium. Electronic address: Myriam.Baes@kuleuven.be.

Abstract

The structural disruption of the mitochondrial inner membrane in hepatocytes lacking functional peroxisomes along with selective impairment of respiratory complexes and depletion of mitochondrial DNA was previously reported. In search for the molecular origin of these mitochondrial alterations, we here show that these are tissue selective as they do neither occur in peroxisome deficient brain nor in peroxisome deficient striated muscle. Given the hepatocyte selectivity, we investigated the potential involvement of metabolites that are primarily handled by hepatic peroxisomes. Levels of these metabolites were manipulated in L-Pex5 knockout mice and/or compared with levels in different mouse models with a peroxisomal β-oxidation deficiency. We show that neither the deficiency of docosahexaenoic acid nor the accumulation of branched chain fatty acids, dicarboxylic acids or C27 bile acid intermediates are solely responsible for the mitochondrial anomalies. In conclusion, we demonstrate that peroxisomal inactivity differentially impacts mitochondria depending on the cell type but the cause of the mitochondrial destruction needs to be further explored.

KEYWORDS:

Bile acids; Mitochondria; Peroxisomes; Respiratory chain; Zellweger; β-oxidation

PMID:
28866057
DOI:
10.1016/j.mito.2017.08.013

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