- 作者: Han-Zen Tsai, Ren-Kuo Lin and Tao-Shih Hsieh
- 作者服務機構: 1. Institute of Cellular and Organismic Biology, Academia Sinica, No. 128, Academia Road, Sec. 2, Nangang, Taipei 11529, R.O.C. 2. Graduate Institute of Life Sciences, National Defense Medical Center, No. 161, Minquan East Road, Sec. 6, Neihu, Taipei 11490, R.O.C.
- 中文摘要: --
- 英文摘要:
Background
Mitochondria play important roles in providing metabolic energy and key metabolites for synthesis of cellular building blocks. Mitochondria have additional functions in other cellular processes, including programmed cell death and aging. A previous study revealed Drosophila mitochondrial topoisomerase III alpha (Top3α) contributes to the maintenance of the mitochondrial genome and male germ-line stem cells. However, the involvement of mitochondrial Top3α in the mitochondrion-mediated aging process remains unclear. In this study, the M1L flies, in which Top3α protein lacks the mitochondrial import sequence and is thus present in cell nuclei but not in mitochondria, is used as a model system to examine the role of mitochondrial Top3α in the aging of fruit flies.
Results
Here, we reported that M1L flies exhibit mitochondrial defects which affect the aging process. First, we observed that M1L flies have a shorter life span, which was correlated with a significant reduction in the mitochondrial DNA copy number, the mitochondrial membrane potential, and ATP content compared with those of both wildtype and transgene-rescued flies of the same age. Second, we performed a mobility assay and electron microscopic analysis to demonstrate that the locomotion defect and mitophagy of M1L flies were enhanced with age, as compared with the controls. Finally, we showed that the correlation between the mtDNA deletion level and aging in M1L flies resembles what was reported in mammalian systems.
Conclusions
The results reported here demonstrate that mitochondrial Top3α ablation results in mitochondrial genome instability and its dysfunction, thereby accelerating the aging process. - 中文關鍵字: --
- 英文關鍵字: Mitochondrial topoisomerase III alpha (mtTop3α), Mitochondria dysfunction, Mitochondrial DNA deletion, Aging