Mitochondrial carrier

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Mitochondrial carriers (MC) form a highly conserved family involved in solute transport across the inner mitochondrial membrane in eukaryotes (57-59). Gene changes comprise the major source of MCF functional diversity (59, 60-63). In HCC, MC homolog 2 has been found to locate in the minimal liver tumor suppressor region within 11p11.2-p12 (64). In addition, high resolution melting analysis had been developed for SLC25A13 mutation scanning. SLC25A13 gene encodes citrin, which is a mitochondrial solute transporter with a crucial role in urea, nucleotide, and protein synthesis. However, researchers did not find that SLC25A13 mutations contributed to the pathogenesis of HCC in Taiwan (65).

In summary, gene-mutation-related mitochondrial dysfunction is involved in the underlying mechanisms of HCC. These genes may play a single role in this process or exhibit multiple functions. For instance, p28GANK-knockdown induces the generation of reactive oxygen species, which in turn activates p38. Because p38 signals Bax, its activation may lead to mitochondrial transmembrane potential loss, cytochrome c release from mitochondria to cytosol, and caspase-9 activation, eventually triggering the mitochondrial pathway of apoptosis (66). These genes that exhibit multiple functions may play a potential role in connecting the mitochondrial apoptosis pathway and other pathways.