TY - JOUR
T1 - Mitochondrial disruption in peroxisome deficient cells is hepatocyte selective but is not mediated by common hepatic peroxisomal metabolites
AU - Shinde, Abhijit Babaji
AU - Baboota, Ritesh Kumar
AU - Denis, Simone
AU - Loizides-Mangold, Ursula
AU - Peeters, Annelies
AU - Espeel, Marc
AU - Malheiro, Ana Rita
AU - Riezman, Howard
AU - Vinckier, Stefan
AU - Vaz, Frédéric M.
AU - Brites, Pedro
AU - Ferdinandusse, Sacha
AU - van Veldhoven, Paul P.
AU - Baes, Myriam
PY - 2018
Y1 - 2018
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.mito.2017.08.013
DO - https://doi.org/10.1016/j.mito.2017.08.013
M3 - Article
C2 - 28866057
SN - 1567-7249
VL - 39
SP - 51
EP - 59
JO - Mitochondrion
JF - Mitochondrion
ER -