Plasmalogens participate in very-long-chain fatty acid-induced pathology.

[zellweger syndrome]

Peroxisomes are organelles responsible for multiple metabolic pathways including , the biosynthesis of plasmalogens , a class of phospholipids , and the beta -oxidation of very -long -chain fatty acids (VLCFA ). Lack of peroxisomes or dysfunction in any of their normal functions is the cellular basis for human peroxisomal disorders . Here we used mouse models to understand and define the biochemical and cellular determinants that mediate the pathophysiological consequences caused by peroxisomal dysfunctions . We investigated the role and effects of cellular plasmalogens and VLCFA accumulation in liver , testis and nervous tissue using Pex 7 and Abcd 1 knockout (KO ) mice . In addition , we also generated a Pex 7 :Abcd 1 double KO mouse to investigate how different peroxisomal dysfunctions modulate cellular function and pathology . We found that plasmalogens function as fundamental structural phospholipids and protect cells from damage caused by VLCFA accumulation . In testis , plasmalogens protect spermatocytes from VLCFA-induced degeneration and apoptosis . In nervous tissue , we found that gliosis , inflammatory demyelination and axonopathy caused by accumulation of VLCFA are modulated by plasmalogens . Our findings demonstrate the importance of normal peroxisomal functioning and allow the understanding of the pathological causality of peroxisomal dysfunctions . Nervous tissue deficient in plasmalogens is more prone to damage , illustrating the importance of plasmalogens in peroxisomal disorders including Zellweger syndrome and X-linked adrenoleukodystrophy .