Proteolytic Control of Lipid Metabolism

ACS Chem Biol. 2019 Nov 15;14(11):2406-2423. doi: 10.1021/acschembio.9b00695. Epub 2019 Sep 30.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Cholesterol / metabolism
  • Gene Expression Regulation
  • Humans
  • Lipid Metabolism
  • Mitochondria / metabolism
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism*
  • Phospholipids / chemistry*
  • Phospholipids / metabolism*
  • Protein Binding
  • Protein Conformation
  • Proteolysis
  • Signal Transduction


  • Phospholipids
  • Cholesterol
  • Peptide Hydrolases