HIGD

HIGD, short for Hypoxia-Induced Gene Domain, refers to a small family of mitochondrial inner membrane proteins found in a wide range of eukaryotes. In humans it comprises two main genes, HIGD1A and HIGD2A, with homologs in many other species. The proteins are typically small and hydrophobic, and they localize to the mitochondrial inner membrane where they are thought to participate in the regulation of mitochondrial respiration, especially under low oxygen conditions.

HIGD1A is upregulated in response to hypoxia through hypoxia-inducible factors and is implicated in helping cells adapt to reduced oxygen availability. It is associated with modulating the activity of the respiratory chain, in particular cytochrome c oxidase (Complex IV), with reported effects on reactive oxygen species production and apoptotic signaling. The precise mechanisms remain under investigation, but HIGD1A is widely cited as part of the mitochondrial response to hypoxic stress.

HIGD2A is less well characterized but is implicated in the assembly or stability of Complex IV. Loss of HIGD2A can impair mitochondrial respiration, suggesting a role in the assembly pathway of cytochrome c oxidase or its maintenance, potentially independent of hypoxic signaling.

Together, HIGD proteins are considered to contribute to the regulation of mitochondrial function during hypoxia and metabolic stress. They exemplify how mitochondria adapt to changing oxygen availability and may have relevance to diseases involving hypoxia, ischemia, or altered metabolism.