Table 7.
Autophagy and mitophagy in the heart (not included in previous tables).
| The models | Ultrastructural changes | Quantitative TEM | References |
|---|---|---|---|
| HL-1 cells under starvation | Starvation ↑ autophagosomes and ↓ mitochondrial content | Mitochondria/cell sections ↓ from 35 to 11 after 3.5 h starvation, and 5 μM CsA correct it to 30; Autophagosomes/cell section ↑ from 0.9 to 3.1 after starvation and CsA corrected it to 15 | Carreira et al., 2010 |
| Adult cardiac progenitor cells in differentiation medium | Knockdown of the mitophagy receptors, Bnip3 and Fundc1 results in the presence of “donut”-shaped mitochondria containing electron-dense areas | No | Lampert et al., 2019 |
| Drosophila muscle and heart | Knockdown of Atg2, Atg9, and Atg18 resulted in elongated mitochondria. The TEM phenotypes were associated with cardiac hypertrophy and shortened life span | No | Xu et al., 2019 |
| Hearts of the Parkin knockout (KO) mice | Smaller mitochondria, ↑Fis1 and ↓ dynamin-related protein 1 (Drp1), oxygen consumption normal in isolated mitochondria. In response to MI, more mitochondrial damage, and accumulation of autophagosomes in Parkin KO mouse hearts at the border zone | Mean mito area 0.5−>0.4 μm2 | Kubli et al., 2013 |
| Tamoxifen inducible Parkin KO (via myh6-MER-cre) | Heart mito in postnatal day 21 (P21) WT mice exhibited ovoid structure compared to P1. Parkin KO P21 mito did not differ from P1, but with abundant lipid droplets (LD) | No | Gong et al., 2015 |
| Whole-body Parkin KO or cardiac (αMHC) Parkin overexpression (OE) | Using a polymerase γ (POLG) mutant mouse that develop cardiac hypertrophy, it was shown that neither Parkin KO or cardiac Parkin OE changed the POLG phenotype, whereas megamitochondria appear to be present in the POLG and the POLG:Parkin OE mice | No | Woodall et al., 2019 |
| Dystrophin-deficient mice (mdx) | ↓ Levels of LC3, P62, Pink1, and Parkin in the mitochondrial fraction; ↑ cristae-damaged mitochondria; ↓ the number of mitochondria in autophagosomes in response to 15 mg/kg DNP (a mitochondrial uncoupler) | At 3–4 months % mitochondria with loss of cristae 0.2−>1/4, at 12 months 1−>3.5 wt vs. mdx After injecting animals with DNP, % mitochondria with loss of cristae 1−> 8 wt vs. mdx; % mitochondria in autophagosomes 0.9−> 0.1 wt vs. mdx |
Kang et al., 2018 |
| AC16 cells with Dox | ↑ Cristae-damaged mitochondria ↑ autophagosomes containing mitochondria |
No | Yin et al., 2018 |
| Rats with lentiviral pigment epithelial-derived factor (PEDF) followed by acute MI (AMI) | AMI ↓ the numbers of mitochondria and ↑ the numbers of mitophagosomes, PEDF further enhanced the change. In neonatal primary cardiomyocytes, PEDF increase cell survival in response to hypoxia, ↓ Parkin, and ↑ ULK1 and FUNDC1. |
Number of mitophagosomes per unit area change from 0 to 2 by AMI, and to 4 if combined with PEDF. The numbers of mitochondria per unit area decreased from 20 to 5 by AMI, and further decreased by PEDF to 2 |
Li et al., 2018 |
Quantification of autophagosomes and mitophagosomes are in bold.