Table 1.

Phenotypic analysis of the mitochondrial Ca²⁺ uniporter complex components after genetic manipulation in the context of a whole organism or a specific tissue

Gene	Specie	Organ/tissue	Genetic perturbation	Phenotype	Refs/source
Mitochondrial Ca2+ influx
MCU	M. musculus	Whole organism (C57BL/6)	KO	Embryonic mortality	IMPC
		Whole organism (C57BL/6xCD1)	KO	Small size Intolerance to strenuous work	Pan et al. (2013)
		Whole organism	KO, single allele	Decreased cardiac stroke volume Increased fasted circulating glucose levels	IMPC
		Skeletal muscle	OE	Skeletal muscle hypertrophy	Mammucari et al. (2015)
			KD	Skeletal muscle atrophy
		Heart	DN – MCU expression	Impaired cathecolamine‐induced heart rate increase	Wu et al. (2015)
			KO	Absent responsiveness to acute stress and “fight‐or‐flight” response Protection from ischaemia/reperfusion injury	Luongo et al. (2015) Kwong et al. (2015)
	D. melanogaster	Mushroom body neurons	KD (during pupation)	Impaired adult memory formation	Drago & Davis (2016)
	D. rerio	Whole organism	KD	Alterations during gastrulation	Prudent et al. (2013)
	C. elegans	Whole organism	KO	Impaired wound healing	Xu & Chisholm (2014)
	T. brucei	Whole organism	KD/KO	Defective growth	Huang et al. (2013)
			OE	Decreased infectivity to mice
MCUb	M. musculus	Whole organism	KO	Impaired righting response Absent vibrissae Increased mean corpuscular volume	IMPC
MCUR1	M. musculus	Heart	KO	Partial perinatal mortality	Tomar et al. (2016)
		Vasculature	KO	Small size Postnatal mortality
MICU1	H. sapiens	Whole organism	Loss‐of‐function mutations	Features of neuromuscular disease Cognitive impairment	Logan et al. (2014)
		Whole organism	Deletion (exon 1)	Early‐onset proximal muscle weakness Exercise‐induced lethargy Confusion	Lewis‐Smith et al. (2016)
	M. musculus	Whole organism (C57BL/6)	KO	Perinatal mortality	Antony et al. (2016)
		Whole organism (C57BL/6N or C57BL/6NxJF1)	KO	Partial perinatal mortality Severe neurological and myophatic complications (in surviving mice)	Liu et al. (2016)
		Liver	KD	Extensive liver inflammation and damage Impaired liver regeneration	Antony et al. (2016)
MICU2	M. musculus	Whole organism	KO	Abnormal active cardiac relaxation Lethal abdominal aortic aneurisms (in hypertensive mice)	Bick et al. (2017)
EMRE	M. musculus	Whole organism	KO	Embryonic mortality	IMPC
	M. musculus (MICU1 −/−)	Whole organism	KO, single allele	Survival (rescue of high perinatal mortality)	Liu et al. (2016)
Mitochondrial Ca2+ efflux
NCLX	M. musculus	Heart	KO	Significant postnatal mortality Cardiac hypertrophy (in surviving mice)	Luongo et al. (2017)

C. elegans, Caenorhabditis elegans; D. melanogaster, Drosophila melanogaster; DN‐MCU, dominant negative MCU; D. rerio, Danio rerio; EMRE, essential MCU regulator; H. sapiens, Homo sapiens; IMPC, International Mouse Phenotyping Consortium; KD, knockdown; KO, knockout; MCU, mitochondrial calcium uniporter; MCUb, mitochondrial calcium uniporter b; MCUR1, mitochondrial calcium uniporter regulator 1; MICU1, mitochondrial calcium uptake 1; MICU2, mitochondrial calcium uptake 2; M. musculus, Mus musculus; NCLX, Li‐permeable Na⁺/Ca²⁺ exchanger; OE, overexpression; T. brucei, Trypanosoma brucei.