Cell Death & Disease

Table 2 Summary of MQC-targeted molecules in diabetic cardiomyopathy.

From: Mitochondrial quality control in diabetes mellitus and complications: molecular mechanisms and therapeutic strategies

In vivo	In vitro	Molecule targets	MQC mechanisms	Reference
HFD-fed mice	HFD-fed mice cardiomyocytes	ATG7 ↓ , PARKIN↓	Inhibiting mitophagy	[122]
STZ-induced mice	Primary NMCMs	PGAM5 ↑ , PHB2 ↓ , DRP1 ↑ , FIS1 ↑ , MFN1 ↓ , MFN2 ↓ , PARKIN ↓ , Beclin1 ↓ , ATG5 ↓ , PGC1α ↓ , NRF2 ↓ , TFAM↓	Promoting fission, inhibiting mitogenesis, fusion and mitophagy	[133, 134]
STZ-induced mice	Primary NRCMs and H9c2 cells with HG	miR-144 ↓ , RAC-1 ↑ , AMPK ↓ , PGC-1α ↓ , NRF1 ↓ , TFAM↓	Inhibiting mitogenesis	[125]
/	Primary NRCMs with HG	CaSR ↓ , GP78 ↑ , MFN1 ↓ , MFN2 ↓ , CX43 ↓ , FIS1 ↑ , DRP1↑	Inhibiting fusion, promoting fission	[126]
Db/db mice	/	PFKFB3 ↓ , NEDD4L, OPA1↓	Promoting fission	[127]
Db/db mice	Primary HCMECs with HG	MAP4K4 ↑ , GPX4 ↓ , SNO-DRP1 ↑ , p-Drp1^S616 ↑ , p-Drp1^S637 ↓	Promoting fission and ferroptosis	[128]
HFD/STZ-induced mice	Primary NMCMs with HG	MST1 ↑ , SIRT3 ↓ , DRP1 ↑ , p-Drp1^S616 ↑ , p-Drp1^S637 ↓ , PARKIN↓	Promoting fission, inhibiting mitophagy	[129, 130]
Db/db mice	H9c2 cells with HG and PA	RCAN1 ↑ , p-Drp1^S616 ↑	Promoting fission	[131]
HFD/STZ-induced mice; db/db mice	Primary neonatal mouse cardiac fibroblasts with HG and HF	ALKBH5 ↓ , YTHDF2 ↑ , NOTCH1 ↓ , ZEB1 ↓ , DRP1↑	Promoting fission	[132]
HFD-fed mice	NMCMs with PA	BRD4 ↑ , PINK1 ↓ , PARKIN ↓ , TIM23 ↑ , VDAC1↑	Inhibiting mitophagy	[133]
HFD/STZ-induced SD rats	H9c2 cells with HG and PA	SFRP2 ↓ , AMPK ↓ , FZD5 ↓ , TFEB ↓ , PGC-1α ↓ , NRF1 ↓ , TFAM ↓ , DRP1 ↑ , FIS1 ↑ , MFN1 ↓ , MFN2 ↓ , PARKIN ↓ , FUNDC1 ↓ , NIX ↓ , BNIP3 ↓ ,	Promoting fission, inhibiting mitogenesis, fusion, and mitophagy	[134, 135]
HFD-fed ZDF rats; db/db mice	Primary NRCMs with HG	ORAI1 ↑ , CnA ↑ , p-ERK1/2 ↑ , DRP1 ↑ , p-Drp1^S616 ↑ , p-Drp1^S637 ↓ , OPA1 ↓ , MFN2↓	Promoting fission, inhibiting fusion	[136]
db/db mice; STZ-induced mice	Primary NRVMs, H9c2 and AC16 cardiomyocytes with HG and PA	DUSP26 ↓ , FAK, ERK, DRP1 ↑ , MFN1 ↓ , MFN2 ↓ , OPA1↓	Promoting fission, inhibiting fusion	[137]
HFD/STZ-induced mice	HL1 cardiomyocytes with HG	LGR6 ↓ , p-STAT3 ↓ , PGC-1α ↓ , cTNI ↑ , MDA ↑ , PTGS2↑	Reducing mitogenesis and mitochondrial respiratory capacity, promoting ferroptosis	[138]
STZ-induced mice	Primary mouse cardiomyocytes with HG	BNP ↓ , PKG ↓ , STAT3 ↓ , OPA1↓	Inhibiting mitochondrial fusion	[139]
HFD/STZ-induced SD rats; db/db mice	Primary NMCMs and H9c2 cells with HG	FOXO1 ↑ , STAT3 ↓ , DRP1 ↑ , MFN1 ↓ , MFN2 ↓ , OPA1 ↓ , PINK1 ↓ , PARKIN↓	Promoting fission, inhibiting fusion, and mitophagy	[140]
Db/db mice	Primary NRCMs with HG, PA and OA	PPARα ↓ , MFN2↓	Promoting fission	[141]
STZ-induced mice	H9c2 cells with HG	ALDH2 ↓ , Akt ↓ , GSK3β ↓ , FOXO3a ↓ , PARKIN↓	Inhibiting mitophagy	[142]

HF high fat, HFD high-fat diet, db/db mice leptin receptor-deficient mice, HG high glucose, STZ streptozotocin, PA palmitic acid, OA oleate acid, SD Sprague Dawley, ZDF Zucker diabetic fat, SNO-Drp1 S-nitrosylation of Drp1, HCMECs human cardiac microvascular endothelial cells, NRCMs neonatal rat cardiomyocytes, NRVMs neonatal rat ventricular myocytes, NMCMs neonatal mouse cardiomyocytes.

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