LIPT2

LIPT2, short for lipoyl(octanoyl) transferase 2, is a human gene that encodes a mitochondrial enzyme involved in the post-translational modification of key mitochondrial enzyme complexes. The protein is believed to participate in the lipoylation pathway, attaching octanoyl groups to specific lysine-containing lipoyl domains on dehydrogenase subunits.

In human cells, lipoic acid is essential for the catalytic activity of several mitochondrial multi-enzyme complexes, including the pyruvate dehydrogenase complex (PDH), the α-ketoglutarate dehydrogenase complex (KGDH), and the branched-chain α-ketoacid dehydrogenase complex (BCKDH). LIPT2 is thought to act as a transferase that transfers an octanoyl moiety to these lipoyl domains, a modification that is subsequently converted into the functional lipoyl cofactor by lipoic acid synthase (LIAS). LIPT2 operates in concert with other lipoylation-related enzymes, such as LIPT1 and LIAS, within mitochondria.

The LIPT2 protein is localized to the mitochondrion and is expressed across tissues, with higher demand in organs with substantial mitochondrial activity. Its structure contains conserved motifs associated with lipoylation-related transferases, reflecting evolutionary conservation with bacterial lipoyltransferases.

Clinical significance in humans is limited but increasingly studied. Rare pathogenic variants in LIPT2 have been reported in individuals with mitochondrial disease–like phenotypes, including metabolic instability and energy-production defects. However, the evidence base is still developing, and more research is needed to define the spectrum of LIPT2-related disorders and the precise molecular mechanisms.

See also lipoylation; LIAS; LIPT1.