Table 2 Regulation of PGAM5 expression.
Gene | Function | Cell type | References | |
---|---|---|---|---|
Gene level | Sp1 | Binds to the PGAM5 promoter and promotes PGAM5 transcription | HK2 cells | |
Stat5 | Binds to the PGAM5 promoter and promotes PGAM5 transcription | N2A neurons; HEK293 cells | ||
miR-21-5p | Specifically binds to the 3′ untranslated region of PGAM5-WT and negatively regulates PGAM5 expression to inhibit mitophagy | AEC-II cells | ||
miR-330 | By inhibiting PGAM5, miR-330 can downregulate mitophagy by inhibiting the PGAM5-induced dephosphorylation of Drp1 | Hepatocytes; primary neurons | ||
Protein level | SIRT2 | Deacetylated PGAM5 | Hepatocellular carcinoma | |
MARCH2 | Interacts directly with PGAM5 and promotes the ubiquitination and degradation of PGAM5 by attaching K48-linked polyUb to the PGAM5 K88 and K141 sites | Cardiomyocytes | ||
XIAP | An E3 ubiquitin ligase that inhibits PGAM5L-mediated cell death by attaching K48-linked polyUb to PGAM5 | HEK293 cells | ||
RNF5 | Degradation of PGAM5 mediated by K48-linked ubiquitination | Hepatocytes | ||
PARL | Cleavage of PGAM5 results in the release of the C-terminal portion of PGAM5 from the mitochondrial membrane | Cortical neurons | ||
OMA1 | The enzyme binds to SLP2 and cleaves PGAM5 in depolarized mitochondria | MEFs | ||
Stx17 | CHD is responsible for binding to the transmembrane structural domain of PGAM5 and regulates the localization of the mitochondrial phosphatase PGAM5 to promote dephosphorylation of Drp1 and mitochondrial fission | 293T cells HeLa cells | ||
KEAP1 | KEAP1 interacts with full-length PGAM5 and controls its degradation in the cytoplasm to inhibit mitophagy | PC6 cells; cortical neurons; HEK293 cells HeLa cells | ||
TIPE3 | TIPE3 recruits PGAM5 to promote BAX and Drp1 accumulation at the mitochondrial cristae, which mediates mitochondrial outer membrane permeabilization, cristae remodeling, mitochondrial fragmentation and apoptosis | Head and neck squamous cell carcinomas (HNSCC) cells | ||
Bcl-xL | Under hypoxic conditions, Bcl-xL interacts with and inhibits PGAM5 to prevent dephosphorylation of the FUNDC1 Ser13 site, which activates hypoxia-induced mitophagy | HeLa cells |