Mitochondrial disruption in peroxisome deficient cells is hepatocyte selective but is not mediated by common hepatic peroxisomal metabolites
| Autor: | Sacha Ferdinandusse, Marc Espeel, Ritesh K. Baboota, Ana R. Malheiro, Howard Riezman, Frédéric M. Vaz, Annelies Peeters, Abhijit Babaji Shinde, Stefan Vinckier, Paul P. Van Veldhoven, Simone Denis, Pedro Brites, Myriam Baes, Ursula Loizides-Mangold |
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| Přispěvatelé: | AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Laboratory Genetic Metabolic Diseases, Other departments, APH - Personalized Medicine, APH - Methodology |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Mitochondrial DNA Respiratory chain Mitochondrion Biology DNA Mitochondrial 03 medical and health sciences medicine Peroxisomes Animals Inner mitochondrial membrane Molecular Biology Mice Knockout Brain Cell Biology Peroxisome Muscle Striated Bile acids Mitochondria 030104 developmental biology medicine.anatomical_structure Electron Transport Chain Complex Proteins Liver Biochemistry Zellweger Β-oxidation Docosahexaenoic acid Hepatocyte Mitochondrial Membranes Knockout mouse ddc:540 Hepatocytes Molecular Medicine |
| Zdroj: | Mitochondrion, Vol. 39 (2018) pp. 51-59 Mitochondrion, 39, 51-59. Elsevier |
| ISSN: | 1567-7249 |
| Popis: | 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. ispartof: Mitochondrion vol:39 pages:51-59 ispartof: location:Netherlands status: published |
| Databáze: | OpenAIRE |
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