Targeting of proteins from the endoplasmic reticulum to lipid droplets: a specific requirement for mitochondrial proteins
Jayson, Christina Brandão Konami
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CitationJayson, Christina Brandão Konami. 2021. Targeting of proteins from the endoplasmic reticulum to lipid droplets: a specific requirement for mitochondrial proteins. Doctoral dissertation, Harvard University Graduate School of Arts and Sciences.
AbstractNeutral lipid storage and metabolism in lipid droplets (LDs) is integral to energy homeostasis in eukaryotic cells. Dysregulation of LDs has been implicated in metabolic diseases including obesity and dyslipidemia. Proteins that localize to LDs play key roles in catalyzing and regulating energy storage and metabolism. Of particular interest, proteins involved in the rate-limiting steps of these processes target LDs from the endoplasmic reticulum (ER) via membrane bridges. Despite the fundamental importance of protein targeting to LDs from the ER, the mechanism by which the ER-LD bridges are formed and proteins gain access to LDs is incompletely understood.
To address this, I first tested the hypothesis that the LD Rab GTPase, Rab18, mediates ER-LD connections to facilitate protein targeting from the ER to LDs, and ultimately determined that Rab18 is not required for LD biogenesis or turnover, and does not play a key role in protein targeting from the ER to LDs. A recent genome wide screen in our lab identified numerous proteins that affect the targeting of a key triglyceride synthesis enzyme to the LD and confirmed that Rab18 is not necessary for ER to LD protein targeting. From this same genome-wide screen, I have investigated the uncharacterized protein, TMEM223, and determined that it is a mitochondrial protein that affects phospholipid homeostasis and ER function. Our results identify an important mitochondrial factor for maintenance of membrane lipid composition and further illustrate how LD phenotypes can be sensitive markers for ER membrane dysfunction.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37368347
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