Table 2.

Effects of experimental modulation of Lonp1 expression on heart and skeletal muscle.

Organ	Experimental Model	Lonp1 Levels	Effects	References
Heart	Mouse cardiomyocytes	Normal expression	Glucose, FAO enzymes and PDH levels modulation in maturing cardiomyocytes	[48]
	Rat cardiomyocyte H9c2 cells	Overexpression	Apoptosis under normoxic conditions	[74,75]
		Downregulation	Mitigation of cell death induced by hypoxia	[74,75]
	Mouse	Knock out	Severe defective heart development; embryonic lethality; Reduction nof cardioprotective effect of IPC; Increment in myocardial infarct size	[66,67,74,75,84]
		Downregulation	fragmentation of mitochondria; cardiomyocytes aberrant metabolic reprogramming; cardiomyopathy; HF	[67]
		Normal expression	Reduction of cardiac stress and injury by reprogramming energy metabolism, thorough the regulation of PDH activity and OXPHOS complexes	[19,24,48,83]
		Upregulation	Reduction of oxidative damage; preservation of redox state of mitochondria; reprograming of mitochondrial bioenergetics; reduction of complex I activity, ROS production, and cardiac cell death	[61]
		Overexpression	Reduction of protein carbonylation and lipid peroxidation during ischemia and early reperfusion	[61,94]
Skeletal muscle	Drosophila	Knockout	Locomotion defects; alteration of respiratory chain function; accumulation of unfolded and oxidized mitochondrial proteins; reduction of OXPHOS capacity and ATP production; stimulation of UPRmt response	[106,107,108,109]
	Mouse C2C12 cells	Knockout	Suppression of PINK1/Parkin pathway; alterations of mitochondrial dynamics; accumulation of damaged mitochondria	[128,129]
	Immortalized mouse myoblasts	Downregulation	Block of autophagy, only at the late stage of myoblast differentiation	[118]
	Mouse myotubes	Knock out	Reduction of fully assembled respiratory complexes IV; alterations of mitochondrial respiration	[101]
	Mouse	Knock out	Alteration of mitochondrial ultrastructure and organelle functions; hypotonia, mild to moderate motor delay; Release of myokines; Reduction of lean and fat mass and lower body weight	[16,25,66,101]
	Mouse under high-fat diet (HFD)	Knock out	Activation of UPRmt; alterations of mitochondrial protein turnover; improvement of insulin resistance; reduction of liver steatosis; prevention of high-fat diet HFD–induced obesity	[135]