Fig. 8.

LPS impacts mitochondrial morphology and function by destabilizing Alcat1. Treatment with LPS activates the HDAC2 deacetylase, which targets Alcat1 at K183. SCF-Fbxo28 docks with deacetylated Alcat1 (in the region of Alcat1 comprising residues 200–250) and catalyzes monoubiquitylation of K183 within Alcat1. Monoubiquitylated Alcat1 is degraded through a lysosomal pathway. Reduction in the cellular concentration of Alcat1 leads to altered cardiolipin content, and impaired mitochondrial structure and bioenergetics. Ac, acetylation; U, ubiquitin.