The Role of Mitochondrial Quality Control in Anthracycline-Induced Cardiotoxicity: From Bench to Bedside

Table 1

MQC-targeted therapeutics in experimental models of AIC.

MQC-targeted agent	Molecular action	Key findings	Experimental objectives	References
Mitochondrial dynamics
Klotho	Downregulator of DRP1	Alleviated mitochondrial fission and apoptosis	In vivo	[194]
Luteolin	Dephosphorylation of Drp1 ^Ser616	Inhibited mitochondrial fission and oxidative stress	In vitro/in vivo	[195]
miRNA-532-3p	Targeting apoptosis repressor with caspase recruitment domain	Attenuated cardiomyocyte mitochondrial fission and apoptosis	In vivo	[107]
Shenmai injection	AMPK & PI3K/Akt/GSK-3β signaling pathway	Alleviated mitochondrial fragmentation and oxidative stress	In vitro/in vivo	[103]
Resveratrol	Activator of Mfn-1 and -2	Prevented left ventricular (LV) remodeling and reduced mitochondrial fragmentation	In vivo	[196]
LCZ696	Angiotensin receptor-neprilysin inhibitor (ARNi)	Attenuated Drp1-mediated mitochondrial dysfunction	In vitro/in vivo	[197]
Mdivi-1	Mitochondrial division inhibitor	Inhibited mitochondrial fission	In vitro/in vivo	[98]
Melatonin	PGC1-α and SIRT1 modulator	Decreased cell death and mitochondrial fission	In vitro/in vivo	[198]
Ciclosporin A	Inhibitor of mitochondrial membrane potential dissipation	Attenuated mitochondrial fragmentation and partially restored mitochondrial bioenergetics	In vivo	[100]
Honokiol	Activator of Sirtuin-3	Promoted mitochondrial fusion	In vitro/in vivo	[199]
Metformin	Activator of AMPK	Improved mitochondrial dynamics balance, biogenesis, and bioenergetics	In vitro/in vivo	[200, 201]
Mitophagy
Heme oxygenase-1	A novel cardioprotective inducible enzyme	Rescued the changes in mitophagy mediators PINK1 and parkin	In vivo	[135]
Donepezil	Acetylcholinesterase inhibitor	Attenuated mitophagy, autophagy, and cardiomyocyte death	In vivo	[202]
Liensinine	A novel mitophagy inhibitor	Inhibited mitophagy and mitochondrial fragmentation	In vivo	[57]
Oseltamivir	Neuraminidase1 inhibitor	Inhibited the expression of Drp1 and PINK1 stabilization on mitochondria, attenuating excessive mitochondrial fission and mitophagy	In vivo	[203]
miRNA-22 knockout	SIRT-1/PGC-1α pathway	Alleviated mitophagy and mitochondrial biogenesis	In vitro/in vivo	[131]
Mitochondrial biogenesis
CO/HO	Activator of Akt1/PKB and guanylate cyclase	Promoted mitochondrial biogenesis and alleviated apoptosis	In vitro/in vivo	[204]
Kirenol	Activator of PI3K/AKT and Nrf2 pathway	Rescued mitochondrial biogenesis and suppressed caspase-dependent apoptosis	In vitro	[205]
Nerolidol	Activator of Nrf2/MAPK signaling pathway	Mitigated oxidative stress, inflammation, and apoptosis	In vivo	[206]
Cyclovirobuxine D	Activator of PGC-1α/Nrf1 signaling pathway	Suppressed oxidative damage and mitochondrial biogenesis	In vivo	[207]
Metallothionein	Activator of PGC-1α/TFAM axis	Preserved mitochondrial biogenesis and MnSOD expression	In vivo	[208]
Yellow wine polyphenolic compounds (YWPC)	Nrf2/TGF-β/smad3 pathway	Mitigated oxidative stress, inflammatory response, and cardiac apoptosis	In vivo	[209]
Cannabidiol	Nonpsychoactive constituent of marijuana	Rescued the Dox-induced cardiac mitochondrial function and biogenesis impairment	In vivo	[210]