Table 8.

Mitochondrial quality control studies using TEM.

The models	Ultrastructural changes	Quantitative TEM?	References
Overexpression (OE) of PGC1α in cardiomyocytes	Adeno-PGC1α in rat neonatal cardiac myocyte resulted in enlarged mitochondria, with ↑ oxygen consumption; MHC-PGC1α mice are fatter, with dilated cardiomyopathy, and ↑ numerous and enlarged mitochondria	Mean total mitochondrial area/total cytoplasmic area in adeno-PGC1α cells was 57% higher relative to control (0.36 vs. 0.23)	Lehman et al., 2000
PGC1α whole body knockout (KO) at 3 months	No specific changes in hypertrophy, dilatation, or fibrosis; normal mitochondria volume despite changes in mitochondrial function	% Mitochondrial volume remained to be ~40%	Arany et al., 2005
PGC1β−/− and double KO (DKO) of PGC1α and 1β	PGC1β−/− appear normal, while DKO resulted in neonatal lethality with heart failure (HF). TEM of the E16.5, E17.5, PD0.5 hearts show lack of increase of heart size showed ↑ of mitochondria in WT, single KO, but not DKO hearts; ↓ mitochondrial volume density and normal myofibril volume density at PD0.5	Mitochondrial volume density from 0.3 to 0.1; myofibril volume density 0.35 μm3/μm3	Lai et al., 2008
Mck-cre mediated PGC1β KO with PGC1α-/–	30% levels of PGC1β mRNA at birth in the heart. Mice start to die at 5 weeks of age with 14% survival by 20 weeks. Progressive cardiomyopathy starting at 1 week of age. Mitochondria appear normal postnatal day 1, fragmentation and elongation abnormality at 1 week, and progressively worsen and also observed ↓ mtDNA, mito protein, and mito function. ↓ Mfn1, Mfn2, Opa1, Fis1 and Drp1, Mitophagosomes were not observed.	No	Lai et al., 2014
Tamoxifen inducible PGC1β cardiac KO with PGC1α-/–	1 month after tamoxifen, TEM shows normal average mitochondrial size or volume density, while ↑ the numbers of mitochondria with cristae damage, with ↓ expression of CDP-diacylglycerol synthase 1, which catalyzes a key step in cardiolipin synthesis	No	Lai et al., 2014; Dorn et al., 2015
Atgl-KO mice	↑ mitochondrial diameter, lipid droplet (LD) and glycogen granule numbers by TEM (10-week-old female), ↓ PGC1α and PGC1β, ↑ glucose/g tissue, ↓ mito size (by FACS), ↓ mtDNA (10-week-old female), impaired mitochondrial respiration (4- and 8-week-old male) in the hearts and led to cardiomyopathy	Mito diameter ~0.55 to ~0.62 μm (~18%) No quantification of LD or numbers of glycogen granules	Haemmerle et al., 2011
αMHC-PGC1α OE through knocking into the ROSA26 locus in both WT and G3Terc−/− (third generation of telomerase deficient) background	The G3Terc−/− mice have ↓ PGC1α levels and deficient mitochondrial function. PGC1α OE in wild-type (WT) mice led to cardiac dysfunction at 12 months and ↓ life span, and in G3 mice ↓ inflammatory cytokines at 10 months TEM studies in 3-month-old WT, PGC1α OE, G3, and G3/PGC1α OE mice demonstrated that PGC1α OE increased mitochondria numbers in both WT and G3 background, at 12 months PGC1α OE in WT mice ↑ distorted mitochondria, at 10 months PGC1α OE in G3 mice ↓ distorted mitochondria	Quantitation were performed at 3 months (but not 10 and 12 months): 10–12.5 mito number/view in WT vs. PGC1α OE 7.5–12 mito number/view in G3 vs. G3/PGC1α OE	Zhu et al., 2019
Estrogen-related receptor (ERR) α and ERRγ DKO with lethal cardiomyopathy	At P16 distorted myofibrils, loss of clear boundaries between the A band and I band, fragmented mitochondria with loss of cristae, ↓ mitochondrial proteins. TEM studies demonstrated ↓ of mitochondrial size and perimeter, some were wrapped by multiple double membranes	Mito Size (μm2): WT ~0.65, DKO ~0.2 Mito Perimeter (μm): ~4.2, DKO ~1.9	Wang et al., 2015
KO of ERRα and ERRγ using AAV9-cTnT-cre	At 5 weeks, there are vesicle engulfed organelles, elongated or fragmented mitochondria and LD in the DKO heart	No	Sakamoto et al., 2020