MTsH

MTsH is a mitochondrial protein that belongs to the TSH family of small membrane-associated proteins. Encoded by the MTsH gene located on chromosome 5p15.33 in humans, the protein is approximately 120 amino acids in length and contains a conserved transmembrane helix followed by a C‑terminal domain that interacts with components of the mitochondrial respiratory chain. MTsH is expressed at high levels in tissues with elevated metabolic demand, such as liver, heart and skeletal muscle, and its expression is up‑regulated in response to oxidative stress.

The primary function of MTsH is to stabilize the activity of complex III of the electron transport chain. Biochemical assays demonstrate that MTsH physically associates with cytochrome b and enhances the electron transfer rate between ubiquinol and cytochrome c. Loss‑of‑function mutations in the MTsH gene are associated with a recessively inherited mitochondrial disorder characterized by infantile-onset hepatopathy, cardiomyopathy and progressive lactic acidosis. In cellular models, MTsH knockdown leads to increased production of reactive oxygen species and impaired ATP synthesis, while overexpression can rescue mitochondrial damage in cells exposed to paraquat.

Structure–function studies have mapped a glycine‑rich motif in the transmembrane region as essential for membrane insertion, while a positively charged patch in the C‑terminal domain mediates interaction with subunit 6 of complex III. Recent crystal structures of MTsH in complex with a synthetic peptide from cytochrome b highlight a hydrogen‑bond network that stabilizes the protein’s orientation within the inner mitochondrial membrane.

MTsH has been the subject of several genome‑wide association studies that implicate common variants in the regulatory region of the gene with susceptibility to non‑alcoholic fatty liver disease in European populations. Further research is needed to clarify its role in other metabolic pathologies and to explore its potential as a therapeutic target for mitochondrial dysfunction.