title: The lipid droplet coat protein perilipin 5 also localizes to muscle mitochondria.
abstract: Perilipin 5 (PLIN5/OXPAT) is a lipid droplet (LD) coat protein mainly present in tissues with a high fat-oxidative capacity, suggesting a role for PLIN5 in facilitating fatty acid oxidation. Here, we investigated the role of PLIN5 in fat oxidation in skeletal muscle. In human skeletal muscle, we observed that PLIN5 (but not PLIN2) protein content correlated tightly with OXPHOS content and in rat muscle PLIN5 content correlated with mitochondrial respiration rates on a lipid-derived substrate. This prompted us to examine PLIN5 protein expression in skeletal muscle mitochondria by means of immunogold electron microscopy and Western blots in isolated mitochondria. These data show that PLIN5, in contrast to PLIN2, not only localizes to LD but also to mitochondria, possibly facilitating fatty acid oxidation. Unilateral overexpression of PLIN5 in rat anterior tibialis muscle augmented myocellular fat storage without increasing mitochondrial density as indicated by the lack of change in protein content of five components of the OXPHOS system. Mitochondria isolated from PLIN5 overexpressing muscles did not possess increased fatty acid respiration. Interestingly though, (14)C-palmitate oxidation assays in muscle homogenates from PLIN5 overexpressing muscles revealed a 44.8% (P = 0.05) increase in complete fatty acid oxidation. Thus, in mitochondrial isolations devoid of LD, PLIN5 does not augment fat oxidation, while in homogenates containing PLIN5-coated LD, fat oxidation is higher upon PLIN5 overexpression. The presence of PLIN5 in mitochondria helps to understand why PLIN5, in contrast to PLIN2, is of specific importance in fat oxidative tissues. Our data suggests involvement of PLIN5 in directing fatty acids from the LD to mitochondrial fatty acid oxidation.
authors: Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Madeleen
authors: M
authors: Bosma
authors: Ronnie
authors: R
authors: Minnaard
authors: Lauren M
authors: LM
authors: Sparks
authors: Gert
authors: G
authors: Schaart
authors: Mario
authors: M
authors: Losen
authors: Marc H
authors: MH
authors: de Baets
authors: Hans
authors: H
authors: Duimel
authors: Sander
authors: S
authors: Kersten
authors: Perry E
authors: PE
authors: Bickel
authors: Patrick
authors: P
authors: Schrauwen
authors: Matthijs K C
authors: MK
authors: Hesselink
mesh_terms: D000328:Adult; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018929:Cell Culture Techniques; D005227:Fatty Acids / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D000070778:Perilipin-1; D000070797:Perilipin-5; D010750:Phosphoproteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats
chemical_list: D002352:Carrier Proteins; D005227:Fatty Acids; D000070778:Perilipin-1; D000070797:Perilipin-5; D010750:Phosphoproteins; C511805:Plin5 protein, mouse; D011506:Proteins