Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kien, B; Kolleritsch, S; Kunowska, N; Heier, C; Chalhoub, G; Tilp, A; Wolinski, H; Stelzl, U; Haemmerle, G.
Lipid droplet-mitochondria coupling via perilipin 5 augments respiratory capacity but is dispensable for FA oxidation
J LIPID RES. 2022; 63(3): 100172
Doi: 10.1016/j.jlr.2022.100172
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- Führende Autor*innen der Med Uni Graz
- Kien Benedikt
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- Abstract:
- Disturbances in lipid homeostasis can cause mitochondrial dysfunction and lipotoxicity. Perilipin 5 (PLIN5) decorates intracellular lipid droplets (LDs) in oxidative tissues and controls tri-acylglycerol (TG) turnover via its interactions with adipose triglyceride lipase and the adipose triglycer-ide lipase coactivator, comparative gene identification-58. Furthermore, PLIN5 anchors mito-chondria to the LD membrane via the outermost part of the carboxyl terminus. However, the role of this LD-mitochondria coupling (LDMC) in cellular energy catabolism is less established. In this study, we investigated the impact of PLIN5-mediated LDMC in comparison to disrupted LDMC on cellular TG ho-meostasis, FA oxidation, mitochondrial respiration, and protein interaction. To do so, we established PLIN5 mutants deficient in LDMC whilst maintaining normal interactions with key lipolytic players. Radiotracer studies with cell lines stably over-expressing wild-type or truncated PLIN5 revealed that LDMC has no significant impact on FA esterifi-cation upon lipid loading or TG catabolism during stimulated lipolysis. Moreover, we demonstrated that LDMC exerts a minor if any role in mitochondrial FA oxidation. In contrast, LDMC significantly improved the mitochondrial respiratory capacity and metabolic flexibility of lipid-challenged cardiomyocytes, which was corroborated by LDMC-dependent interactions of PLIN5 with mitochondrial proteins involved in mitochondrial respiration, dynamics, and cristae organization. Taken together, this study suggests that PLIN5 preserves mitochondrial function by adjusting FA supply via the regulation of TG hydro-lysis and that LDMC is a vital part of mitochondrial integrity.
- Find related publications in this database (Keywords)
- PLIN5
- lipid droplets
- lipolysis
- mitochondrial respiration
- FA oxidation
- lipid droplet-mitochondria coupling
- adipose-triglyceride lipase
- comparative gene identification-58
- lipotoxicity
- cardiovascular disease