Aging is Associated with a Decline in Atg9b‐mediated Autophagosome Formation and Appearance of Enlarged Mitochondria in the Heart
| العنوان: | Aging is Associated with a Decline in Atg9b‐mediated Autophagosome Formation and Appearance of Enlarged Mitochondria in the Heart |
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| المؤلفون: | Alexandra G. Moyzis, Åsa B. Gustafsson, Rita H. Najor, Mark A Lampert, Wenjing Liang, Rachel Y. Diao |
| المصدر: | Aging Cell |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Autophagosome, Male, autophagy, Aging, Mitochondrial Turnover, Autophagy-Related Proteins, Biology, Mitochondrion, Biochemistry, Parkin, Mitochondria, Heart, 03 medical and health sciences, Mice, 0302 clinical medicine, Mitophagy, Genetics, Animals, Humans, Enlarged mitochondria, Molecular Biology, Original Paper, Chemistry, Myocardium, Autophagy, Autophagosomes, Membrane Proteins, Heart, Cell Biology, Autophagosome formation, Cell biology, mitochondria, 030104 developmental biology, mitophagy, Mitochondrial biogenesis, Mitochondrial fission, 030217 neurology & neurosurgery, Atg9, HeLa Cells, Biotechnology |
| الوصف: | Advancing age is a major risk factor for developing heart disease, and the biological processes contributing to aging are currently under intense investigation. Autophagy is an important cellular quality control mechanism that is reduced in tissues with age but the molecular mechanisms underlying the age‐associated defects in autophagy remain poorly characterized. Here, we have investigated how the autophagic process is altered in aged mouse hearts. We report that autophagic activity is reduced in aged hearts due to a reduction in autophagosome formation. Gene expression profile analysis to evaluate changes in autophagy regulators uncovered a reduction in Atg9b transcript and protein levels. Atg9 proteins are critical in delivering membrane to the growing autophagosome, and siRNA knockdown of Atg9b in cells confirmed a reduction in autophagosome formation. Autophagy is also the main pathway involved in eliminating dysfunctional mitochondria via a process known as mitophagy. The E3 ubiquitin ligase Parkin plays a key role in labeling mitochondria for mitophagy. We also found increased levels of Parkin‐positive mitochondria in the aged hearts, an indication that they have been labeled for mitophagy. In contrast, Nrf1, a major transcriptional regulator of mitochondrial biogenesis, was significantly reduced in aged hearts. Additionally, our data showed reduced Drp1‐mediated mitochondrial fission and formation of enlarged mitochondria in the aged heart. Overall, our findings suggest that cardiac aging is associated with reduced autophagosome number, decreased mitochondrial turnover, and formation of megamitochondria. Here, we report that autophagic activity is reduced in aged hearts due to decreased expression of the autophagy‐related protein Atg9b. This protein is involved in delivering membrane to form and expand the autophagosome. Our findings also demonstrate that there is an imbalance in the labelling and degradation steps in the aged myocardium due to reduced formation of autophagosomes. The decline in mitochondrial clearance also coincides with formation of megamitochondria in aged hearts. |
| تدمد: | 1530-6860 0892-6638 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9c97a496eb92b3a42548bee90e0ee290Test https://doi.org/10.1096/fasebj.2021.35.s1.02609Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9c97a496eb92b3a42548bee90e0ee290 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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