PPARGC1 and ESRR-induced regulator in muscle 1 (PERM1) (PERM1)

PPARGC1 and ESRR-induced regulator in muscle 1 (PERM1) is a protein primarily expressed in skeletal and cardiac muscle that acts as a critical regulator of mitochondrial biogenesis and oxidative metabolism (Cho et al., 2013, PMID: 23836911). It is transcriptionally induced by the coactivator PGC-1alpha and the estrogen-related receptors (ERRs), forming a feed-forward loop that enhances the expression of genes involved in energy production and oxidative phosphorylation (UniProt, Q5SVL3). PERM1 is essential for maintaining mitochondrial integrity and metabolic homeostasis; its downregulation is linked to the progression of heart failure and skeletal muscle atrophy (Watanabe et al., 2022, PMID: 35105615). In the heart, PERM1 supports the high energy demands of contraction by regulating the tricarboxylic acid cycle and fatty acid oxidation (Cho et al., 2015, PMID: 25605811). Although no specific drugs targeting PERM1 are currently in clinical use, it is considered a promising therapeutic target for metabolic and cardiovascular diseases where mitochondrial dysfunction is a key driver (Cho et al., 2013, PMID: 23836911). Future therapeutic approaches may focus on small molecules that stabilize PERM1 or gene therapy to restore its levels in diseased tissues. Its role in muscle thermogenesis and exercise capacity further highlights its potential in treating metabolic syndrome and obesity-related complications. Research indicates that PERM1 interacts with the MICOS complex to maintain mitochondrial cristae structure, which is vital for efficient ATP production (Watanabe et al., 2022, PMID: 35105615).

Other names

C1orf170PGC-1 and ERR-induced regulator in muscle protein 1PERM-1

Enhancement of PGC-1alpha and ESRR-mediated transcriptional activity to promote mitochondrial gene expression (Cho et al., 2013, PMID: 23836911).