Drosophila models of peroxisomal biogenesis disorder: peroxins are required for spermatogenesis and very-long-chain fatty acid metabolism.
Peroxisomes are vital eukaryotic organelles that participate in lipid metabolism, in particular the metabolism of very-long-chain fatty acids (VLCFA). The biogenesis of peroxisomes is regulated by a set of peroxin proteins (PEX). In humans, mutations affecting peroxin protein production or function result in devastating diseases classified as peroxisome biogenesis disorders (PBD). The way in which peroxisomal dysfunction leads to the pathophysiological consequences of PBD is not well understood. Here we report that Drosophila pex mutants faithfully recapitulate several key features of human PBD, including impaired peroxisomal protein import, elevated VLCFA levels and growth retardation. Moreover, disruption of pex function results in spermatogenesis defects, including spermatocyte cytokinesis failure in Drosophila. Importantly, increased VLCFA levels enhance these spermatogenesis defects whereas reduced VLCFA levels alleviate them. Thus, regulation of proper VLCFA levels by pex genes is crucial for spermatogenesis. Together our study reveals an indispensable function of pex genes during spermatogenesis and provides a causative link between the phenotypic severity of pex mutants and VLCFA levels.
Chen
Haiyang
H
Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Liu
Zhonghua
Z
Huang
Xun
X
D000818:Animals; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D018901:Peroxisomal Disorders / Q000235:genetics / Q000378:metabolism*; D013090:Spermatocytes / Q000254:growth & development / Q000378:metabolism; D013091:Spermatogenesis
D029721:Drosophila Proteins; D005227:Fatty Acids