Table I.

Summary of key proteins involved in mitochondrial protein trafficking, mitophagy and dynamics and alterations in their expression/function in heart failure. (Idiopathic) dilated cardiomyopathy (DCM), Ischemic cardiomyopathy (ICM), Hypertrophic cardiomyopathy (HCM), OMM: outer mitochondrial membrane, IMM: inner mitochondrial membrane.

Name	Location	Function	ICM	DCM	TAC and Hypertension Induced HF
Mitochondrial Trafficking
TOM/TIM	TOM:OMM TIM:IMM	Protein import & sorting		Defect in Pam18 (Tim14) is involved in dilated cardiomyopathy with ataxia (DCMA), by human genome mapping (39).	Tom70 was downregulated in pathological hypertrophic hearts from humans and experimental animals (101).
mtHSP70 (Grp75)	Matrix	Chaperone. Interacts with TIM44 (113) Maintains mtDNA	-	-	-
mtHSP40	Matrix	Chaperone. Maintains mtDNA	-	Mice deficient in Dnaja3 developed DCM and died before 10 weeks of age, at least in part, through its chaperone mtHSP40 activity (72).	-
MPTP	IMM	Non-selective pore for molecules d1.5 kDa	Inhibition of MPTP opening attenuated cardiac ischemic-reperfusion injury in mice (93).	Increased MPTP opening in Drp1 null mitochondria was associated with mitophagy in MEFs and contributed to cardiomyocyte necrosis and dilated cardiomyopathy in mice (178).	Prevention of MPTP opening is protective in patients with obstructive hypertrophic cardiomyopathy (153).
HSP60	Matrix&Cytosol		Increased in IHF in rat and human (89, 105); Abnormal Localization to plasma membrane associated with increased apoptosis (105). Mt HSP60 unchanged in rat IHF(109). Decreased HSP60 in LV cytoplasmic fraction and increased HSP60 in LV mitochondrial fraction in LV (105, 170). Increased in blood in human ICM (115).	Levels of hsp60 doubled in DCM (89). Decrease of HSP60 level in cytoplasmic fraction and increase of HSP60 in LV mitochondrial fractions (170). Increased HSP60 protein level and mRNA level in patients with DCM (95).
Autophagy/Mitophagy
Parkin	Cytosol	Protein degradation		Dysfunction of PINK-Parkin interaction leads to dilated cardiomyopathy in Mfn2-deficient mouse embryonic fibroblasts and cardiomyocytes and in Parkin-deficient Drosophila heart tubes (34).	-
P53	Matrix&Cytosol	Transcription factor regulated by cell stress, including DNA damage and hypoxia. Regulates genes involved in cell cycle arrest, DNA repair, senescence, apoptosis		Inhibition of p53 leads to dilated cardiomyopathy in adult mice cardiomyocytes (198) Accumulation of P53 leads to DCM through CaMKIIδ in mice (184).
PINK1	OMM	Mitophagy	-	Dysfunction of PINK-Parkin interaction leads to dilated cardiomyopathy in Mfn2-deficient mouse embryonic fibroblasts and cardiomyocytes and in Parkin-deficient Drosophila heart tubes (34).	PINK1−/− mice develop left ventricular dysfunction and evidence of pathological cardiac hypertrophy as early as 2 mo of age (15)
P62	Cytosol	Mitophagy	Increased in human cardiomyocytes from patients with ICM (35).	Increased in human cardiomyocytes from patients with DCM (35).	Expression of p62 was decreased in Mdivi (mitochondrial division inhibitor) treated TAC mice compared to controls (63). Fission inhibition ameliorates development of HF after TAC (63).
Fission & Fusion
OPA1	IMM	Fusion	Expression of OPA1, was decreased in in rat and human ICM (32).	No difference in human DCM (32).	-
Mfn1	OMM	Mitofusins, mitophagy	No difference in ICM rat. Increased in human ICM (32).	Increased in human DCM (32).	-
Mfn2	OMM	Mitofusins, mitophagy Mfn2 functions as a mitochondrial receptor for Parkin and is required for quality control of cardiac mitochondria	No difference in IHF rat. Increased in human ICM (32).	Increased in human DCM (32).	Mfn2 was decreased in phenylephrine induced hypertrophy in neonatal rat ventricular myocytes, hypertrophied hearts from spontaneously hypertensive rats, and mice with pressure-overload induced hypertrophy by TAC (1 and 3 weeks). Mfn2 was not decreased in hypertrophied hearts after 15 weeks of TAC, nor in hypertrophied non-infarcted myocardium following MI (52)
Drp1	OMM	Fission	No difference in IHF rat. Increased in human ICM (32).	Increased in human DCM (32). Conditional cardiomyocyte-specific Drp1 ablation evoked mitochondrial enlargement, lethal dilated cardiomyopathy, and cardiomyocyte necrosis (178).	Drp1 was phosphorylated in pressure overload induced hypertrophy in TAC mouse hearts and phenylephrine (PE)-treated rat neonatal cardiomyocytes (27). Mutation of Drp1 leads to myocyte hypertrophy (8).
Fis1	OMM	Fission	No difference in IHF rat. No difference in human ICM (32).	No difference in DCM (32).
Oxidative Respiration
NDUFA5	IMM	Complex I ETC	Decreased in mitochondria in LV of IHF rat (109).
NDUFV1	IMM	Complex I ETC	Decreased in mitochondria in LV of IHF rat (109).	Decreased in patients with DCM (141).	Decreased significantly in TAC mice, and restored in TAC after stem cell treatment (199).
Mn-SOD	matrix	Free-radical scavenger		The null mice develop dilated cardiomyopathy and die within 10 days after birth (103).	Zn–SOD was markedly decreased in Copper Deficiency mice which leads to hypertrophic cardiomyopathy (48).