PEX19 Coordinates Neutral Lipid Storage in Cells in a Peroxisome-Independent Fashion

• DOI: 10.3389/fcell.2022.859052
• Publication Date: 2022-04-26T05:36:42Z
• Authors: Sven Lyschik; Anna A. Lauer; Tanja Roth; Daniel Janitschke; Markus Hollander; Thorsten Will; Tobias Hartmann; Ron R. Kopito; Volkhard Helms; Marcus O. W. Grimm; Bianca Schrul
• Keywords: Organelle; Peroxisomal disorder

Cellular lipid metabolism is tightly regulated and requires a sophisticated interplay of multiple subcellular organelles to adapt changing nutrient supply. PEX19 was originally described as an essential peroxisome biogenesis factor that selectively targets membrane proteins peroxisomes. Metabolic aberrations were associated with compromised functions, solely attributed the absence peroxisomes, which also considered underlying cause for Zellweger Spectrum Disorders. More recently, however, it shown mediates targeting VCP/P97-recuitment UBXD8 ER from where partitions droplets (LDs) but physiological consequences remained elusive. Here, we addressed intriguing possibility coordinates functions major cellular sites metabolism. We exploited farnesylation deciphered organelle-specific using systems level approaches. Non-farnesylated sufficient fully restore metabolic activity while farnesylated controls by peroxisome-independent mechanism can be sorting specific protein subset LDs. In this PEX19-dependent LD proteome, cells accumulate excess triacylglycerols fail deplete their neutral stores under catabolic conditions, highlighting hitherto unrecognized function in controlling storage dynamics.