Table 1.

Effects of UPR^mt signaling components on metabolic phenotypes in mammals.

Function	Gene name	Protein name	Metabolic phenotype	References
Chaperone	Hspd1	HSPD1	Reduction in hypothalamus of obese and diabetic subjects; Increase of myocardial Hspd1 in high-fructose fed rats; knockdown induces diabetes-mediated renal tubular dysfunction	Kleinridders et al. (2013), Aluksanasuwan et al. (2017)
	Trap1	TRAP1	Decrease of obesity and tumor formation in TRAP1 knockout	Lisanti et al. (2014)
	Phb	PHB	Overexpression in adipocytes leads to obesity in both genders, but impairment in glucose homeostasis only in male mice	Dong et al. (2013), Ande et al. (2014)
	Hspa1a	HSP72	Lower muscular Hsp72 expression in patients with T2DM. Overexpression enhances energy expenditure and insulin sensitivity. Knockout induces obesity and insulin resistance	Kurucz et al. (2002), Bruce et al. (2003), Drew et al. (2014), Henstridge et al. (2014)
Protease	Oma1	OMA1	Increased body weight and fat content, improved glucose tolerance and insulin sensitivity on NCD, but loss of metabolic benefits on HFD. Restoration of cardiac function in Yme1l1-deficient mice	Quiros et al. (2012)
	Lonp1	LON	Increased hepatic gluconeogenesis	Lee et al. (2011), Ngo et al. (2011)
	Clpp	CLPP	Amelioration of cardiomyopathy	Seiferling et al. (2016)
	Yme1l1	YME1L1	Induces dilated cardiomyopathy and heart failure	Wai et al. (2015)
	Parl	PARL	Impaired insulin signaling in skeletal muscle	Walder et al. (2005), Civitarese et al. (2010)
Mitokine	Gdf15	GDF15	GDF15 levels in serum increase in patients with T2DM. Associated with fatty acid oxidation and lipolysis. Reduces liver injury by modulating immune cell infiltration	Dostalova et al. (2009), Kempf et al. (2012), Hong et al. (2014), Chung et al. (2017a ,b)
	Adm2	ADM2	Negative correlation with body weight. Overexpression in adipocytes induces beiging of white adipose tissue as well as M2 polarization of adipose macrophages. Recombinant ADM2 inhibits insulin resistance by deactivating adipose CD4+ T cells	Lv et al. (2016), Zhang et al. (2016)
	Angptl6	ANGPTL6	Required for Fgf21 expression in adipocytes. Increases insulin sensitivity, glucose tolerance and energy expenditure	Oike et al. (2005), Kang et al. (2017)
	Fgf21	FGF21	Increases fat oxidation and mitochondrial function. Enhances glucose uptake in muscle and browning in white adipose tissue. Attenuates diabetic cardiomyopathy	Fisher et al. (2012), Kim et al. (2013), Vandanmagsar et al. (2016), Wu et al. (2017)

HFD, high-fat diet; NCD, normal chow diet; T2DM, type 2 diabetes mellitus.