TY - JOUR
T1 - Proteolytic Control of Lipid Metabolism
AU - Sam, Pingdewinde N.
AU - Avery, Erica
AU - Claypool, Steven M.
N1 - Funding Information:
We gratefully acknowledge W. Shao and P. Espenshade for assistance in proofreading the Proteolytic Control of Cholesterol Metabolism section. P.N.S. and E.A. also thank former and current members of the Claypool lab. This work was supported by the National Institutes of Health (Grant R01GM111548 to S.M.C.) and the National Science Foundation Graduate Research Fellowship Program (DGE1746891 to P.N.S.).
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/11/15
Y1 - 2019/11/15
N2 - Synthesis and regulation of lipid levels and identities is critical for a wide variety of cellular functions, including structural and morphological properties of organelles, energy storage, signaling, and stability and function of membrane proteins. Proteolytic cleavage events regulate and/or influence some of these lipid metabolic processes and as a result help modulate their pleiotropic cellular functions. Proteins involved in lipid regulation are proteolytically cleaved for the purpose of their relocalization, processing, turnover, and quality control, among others. The scope of this review includes proteolytic events governing cellular lipid dynamics. After an initial discussion of the classic example of sterol regulatory element-binding proteins, our focus will shift to the mitochondrion, where a range of proteolytic events are critical for normal mitochondrial phospholipid metabolism and enforcing quality control therein. Recently, mitochondrial phospholipid metabolic pathways have been implicated as important for the proliferative capacity of cancers. Thus, the assorted proteases that regulate, monitor, or influence the activity of proteins that are important for phospholipid metabolism represent attractive targets to be manipulated for research purposes and clinical applications.
AB - Synthesis and regulation of lipid levels and identities is critical for a wide variety of cellular functions, including structural and morphological properties of organelles, energy storage, signaling, and stability and function of membrane proteins. Proteolytic cleavage events regulate and/or influence some of these lipid metabolic processes and as a result help modulate their pleiotropic cellular functions. Proteins involved in lipid regulation are proteolytically cleaved for the purpose of their relocalization, processing, turnover, and quality control, among others. The scope of this review includes proteolytic events governing cellular lipid dynamics. After an initial discussion of the classic example of sterol regulatory element-binding proteins, our focus will shift to the mitochondrion, where a range of proteolytic events are critical for normal mitochondrial phospholipid metabolism and enforcing quality control therein. Recently, mitochondrial phospholipid metabolic pathways have been implicated as important for the proliferative capacity of cancers. Thus, the assorted proteases that regulate, monitor, or influence the activity of proteins that are important for phospholipid metabolism represent attractive targets to be manipulated for research purposes and clinical applications.
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U2 - 10.1021/acschembio.9b00695
DO - 10.1021/acschembio.9b00695
M3 - Review article
C2 - 31503446
AN - SCOPUS:85073101942
SN - 1554-8929
VL - 14
SP - 2406
EP - 2423
JO - ACS chemical biology
JF - ACS chemical biology
IS - 11
ER -