Mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis. Terminal step in leucine catabolism. Ketone bodies (beta-hydroxybutyrate, acetoacetate and acetone) are essential as an alternative source of energy to glucose, as lipid precursors and as regulators of metabolism. (3S)-hydroxy-3-methylglutaryl-CoA = acetoacetate + acetyl-CoA Metabolic intermediate metabolism; (S)-3-hydroxy-3-methylglutaryl-CoA degradation; acetoacetate from (S)-3-hydroxy-3-methylglutaryl-CoA: step 1/1. Homodimer; disulfide-linked. Can also form homotetramers. Unprocessed form is peroxisomal. In suckling rat, highest levels in liver and in intestine. Lower levels in heart, kidney and cerebellum. Weak expression in brain cortex, medulla and midbrain. Levels decrease slightly during weaning. Belongs to the HMG-CoA lyase family.