Table 1. Highlight of most relevant data discussed in the review for the understanding of interactions between mitochondrial and skeletal muscle biology in the contest of mitochondrial myopathy.

	Highlighted data	Organism	Reference
	1. Metabolic remodelling
	Mitochondrial specialisation between fibre types	Human	[29]
	Proteomics changes between COX-negative and -positive fibres	Human	[30]
	CI subunits deficiency with m3243.A > G mutation	Human	[32]
	CI and CIV subunits deficiency with single, large-scale mtDNA deletion	Human	[21,33]
	CII and CV subunit increase with single, large-scale mtDNA deletion	Human	[33]
	Starvation-like response with multiple mtDNA deletions	Deletor mice, human,	[35,36]
	Mitochondrial integrated stress response with multiple mtDNA deletions	Deletor mice	[39]
	Remodelling of one-carbon pathways with multiple mtDNA deletions	Deletor mice, human	[40]
	Starvation-like response with m.8344A > G mutation and in COX10 deficiency	COX10 KO mice, human	[48,49]
	Metabolic remodelling in reversible infantile respiratory chain deficiency	Human	[53,54]
	Compensatory metabolism of lactate with severe mitochondrial myopathy phenotye	Ndufs4 KO mice, muscle specific type II fibres Mfn1/Mfn2 KO, human	[63,64,66,67]
	Succinate as a skeletal muscle remodelling modifier	Wild-type mice	[71,72]
	Rapamacin as an effective treatment	Muscle specifc Cox15 KO mice, Deletor mice, human	[39,135,141]
	Nicotinamide riboside and niacin as an effective treatment	Deletor mice, human	[41,47]
	Hypoxia as an effective therapy	Cells, zebrafish model, Leigh syndrome mice	[66,67]
	2. Mitochondrial morphology
	Link between cristae morphology and cell specific metabolism	Worm, flies, mice, human	[83,84]
	Differential morphology and metabolism between subsarcolemmal and perinuclear mitochondria and intermyofibrillar mitochondria	Human	[86–88]
	Continuous mitochondrial network for efficient energy distribution	Wild-type mice	[91,92]
	Decreased cristae density with mitochondrial dysfunction	Cells	[99]
	Donut mitochondria, concentric cristae, paracrystalline inclusions with mitochondria dysfunction	Human	[97]
	Increased number of nanotunnels with mitochondria dysfunction	Human	[96,97]
	Mitochondrial network fragments with higher mtDNA mutation load	Cells, human	[84,93]
	3. Mitochondrial turnover
	Fibre type switching and exercise intolerance	PGC-1α KO mice	[117]
	Decreased levels of oxidative phosphorylation and fatty acids oxidation	Surf1 KO mice, Sco2 KO/KIN, muscle-specific Cox15 KO, Deletor mice	[41,118,120]
	Activation of mitochondrial biogenesis after treatment	Surf1 KO mice, Sco2 KO/KIN, muscle-specific Cox15 KO, human	[41,47,118,122,123,124,125]
	Activation of perinuclear mitochondrial biogenesis in mitochondrial dysfunction	Human	[16]
	Activation of UPRmt within the fibre and in the perinuclear area	Human	[16,41]
	AICAR as an effective treatment	KO/KI, muscle-specific Cox15 KO	[118]
	Bezafibrate as a potential effective treatment	Deletor mice, human	[122,123,124,125]
	Mitophagy and autophagy impairment with both mtDNA deletions and point mutations	Muscle-specific Cox15 KO, human	[130,133,134]
	Mitophagy impairment with stage-wise dynamics	Parkin KO flies, PINK1 KO flies, Deletor mice, human	[16,135,138]
	Restore of mitophagy and autophagy by rapamycin treatment	Muscle-specific Cox15 KO, Deletor mice, human	[39,134,135]
	Modulation of mTORC1 and mitophagy and rapamycin dose-dependency	Coq9R239X mice	[140]
4. Cellular processes
Apoptosis	Myofibres apoptosis in atrophy or myopathy	Mice models, human	[148]
	Correlation of apoptosis to high mtDNA mutation load and respiratory chain deficiency	Human	[149,150]
	High rate of apoptosis in myofibres displaying mitochondrial myopathy	Human	[149,151,152,156–158]
ROS production	Associated ROS over-production to oxidative phosphorylation defects	Ant1 KO mice, human	[153,166,169]
	Increased antioxidant enzymes to ROS over-production	Ant1 KO mice, human	[166–168]
	ROS over-production as a disease modifier for satellite cells, mitophagy, autophagy	Cells, mice, human	[172–175]
Ca2+ signalling	Impairment of Ca2+ uptake capacity due to decrease in porin	Human	[21,31–33]
	Modulation of TCA cycle by Ca2+ handling	Cardyomyocites, human	[177,178,184–187]
	CIV or CV deficiency linked to impaired mitochondria-ER contact sites, UPRmt and UPR and different contraction patterns	Cells, Drp1 KO mice, human	[191–193,197,198]
Novel mitochondrial process	Excess of mtDNA copy number to sense and modulate mitochondrial homeostasis	Cells, Tfam+/− mice	[199,200]
	mtDNA molecules extrusion under oxidative stress conditions, apoptosis or in mitochondrial myopathy	Cells, human	[97,202,203]
	mtDNA detection in a cell-free state with paracrine/endocrine role	Human serum and plasma	[208]
	Mitochondrial-derived vescicles for mitochondrial turnover and regenerative potential in skeletal muscle	Cells, mice models, human	[209–212]
	5. Muscle cell morphology and function
	Impact of mitochondrial morphology onto myofibrillar morphology and branching	Wild-type flies	[214]
	Link bewteen size/position of mitochondria and the cross-sectional area of myosin fibrilis/muscle	Wild-type flies, wild-type mice and rats, human	[216,218]
	Sarcolemmal distension and disruption of myofibrillar organisation in ragged-red fibres due to increased subsarcolemmal and intermyofibrillar mitochondria	Human	[97]
	Disruption of myofibrils and skeletal muscle dysfunction in mitochondrial dysfunction	Human	[217]
	Mitochondrial fusion and fission reduction with sarcopenia	Rats, muscle-specific Opa1 KO mice, human	[30,219,220]
	High level of mtDNA in mitochondria dysfunction only in a small portion of muscle fibres with atrophy	Deletor mice, rats, human	[222,223,224]
	Central nuclei and nucleophagy adjacent to clusters of lysosomes, mitochondria and mitolysosomes	Human	[135,225]