Table 2 Regulation of PGAM5 expression.

From: The dual role of PGAM5 in inflammation

 

Gene

Function

Cell type

References

Gene level

Sp1

Binds to the PGAM5 promoter and promotes PGAM5 transcription

HK2 cells

29

Stat5

Binds to the PGAM5 promoter and promotes PGAM5 transcription

N2A neurons; HEK293 cells

39

miR-21-5p

Specifically binds to the 3′ untranslated region of PGAM5-WT and negatively regulates PGAM5 expression to inhibit mitophagy

AEC-II cells

85

miR-330

By inhibiting PGAM5, miR-330 can downregulate mitophagy by inhibiting the PGAM5-induced dephosphorylation of Drp1

Hepatocytes; primary neurons

11,98

Protein level

SIRT2

Deacetylated PGAM5

Hepatocellular carcinoma

30

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

32

XIAP

An E3 ubiquitin ligase that inhibits PGAM5L-mediated cell death by attaching K48-linked polyUb to PGAM5

HEK293 cells

33

RNF5

Degradation of PGAM5 mediated by K48-linked ubiquitination

Hepatocytes

31

PARL

Cleavage of PGAM5 results in the release of the C-terminal portion of PGAM5 from the mitochondrial membrane

Cortical neurons

16,34

OMA1

The enzyme binds to SLP2 and cleaves PGAM5 in depolarized mitochondria

MEFs

35

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

23

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

104

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

36

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

105