AI Article Synopsis
- Mitochondrial dynamics and mitophagy are crucial for heart and brain health, particularly in the context of diseases like cardiovascular and neurodegenerative disorders.
- Mice lacking the protein Drp1, essential for mitochondrial division, faced severe heart defects and showed increases in mitochondrial connectivity, protein accumulation, and reduced respiration.
- The study highlights that the function of parkin, a protein linked to Parkinson's disease, differs from traditional views, as its role in ubiquitinating mitochondrial proteins is independent of Drp1 in the heart, and the absence of both proteins leads to worse cardiac issues and affects neuronal health.
Article Abstract
Mitochondrial dynamics and mitophagy have been linked to cardiovascular and neurodegenerative diseases. Here, we demonstrate that the mitochondrial division dynamin Drp1 and the Parkinson's disease-associated E3 ubiquitin ligase parkin synergistically maintain the integrity of mitochondrial structure and function in mouse heart and brain. Mice lacking cardiac Drp1 exhibited lethal heart defects. In Drp1KO cardiomyocytes, mitochondria increased their connectivity, accumulated ubiquitinated proteins, and decreased their respiration. In contrast to the current views of the role of parkin in ubiquitination of mitochondrial proteins, mitochondrial ubiquitination was independent of parkin in Drp1KO hearts, and simultaneous loss of Drp1 and parkin worsened cardiac defects. Drp1 and parkin also play synergistic roles in neuronal mitochondrial homeostasis and survival. Mitochondrial degradation was further decreased by combination of Drp1 and parkin deficiency, compared with their single loss. Thus, the physiological importance of parkin in mitochondrial homeostasis is revealed in the absence of mitochondrial division in mammals.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282557 | PMC |
| http://dx.doi.org/10.15252/embj.201488658 | DOI Listing |
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