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Altered Mitochondrial Function and Accelerated Aging Phenotype in Neural Stem Cells Derived from Dnm1l Knockout
Seung-Bin Na1, Bong-Jong Seo1, Tae-Kyung Hong1
1Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.
International Journal of Molecular Sciences
|September 28, 2023
Summary
Mitochondrial fission, regulated by dynamin 1-like protein (Dnm1l), is vital for neural stem cell (NSC) function. Dnm1l deficiency impairs NSC self-renewal and accelerates aging due to mitochondrial defects.
Area of Science:
- Cellular Biology
- Mitochondrial Dynamics
- Neuroscience
Background:
- Mitochondria are essential for cellular energy, signaling, aging, and death.
- Mitochondrial dynamics, including fission and fusion, allow cells to adapt.
- Dynamin 1-like protein (Dnm1l) is a key regulator of mitochondrial fission.
Purpose of the Study:
- To investigate the impact of dynamin 1-like protein (Dnm1l) gene knockout on neural stem cells (NSCs).
- To analyze mitochondrial morphology, function, and cellular behavior in Dnm1l-deficient NSCs.
Main Methods:
- Neural stem cells (NSCs) were differentiated from Dnm1l knockout embryonic stem cells (Dnm1l-/- ESCs).
- Morphology, NSC marker expression (Sox2, Nestin, Pax6), mitochondrial function, and cellular aging markers were assessed.
- Comparison was made between Dnm1l-/- NSCs, wild-type ESC-derived NSCs (WT-NSCs), and brain-derived NSCs.
Main Results:
- Dnm1l-/- NSCs displayed elongated mitochondria, reduced respiratory capacity, and a metabolic shift to glycolysis.
- These cells showed impaired self-renewal, accelerated cellular aging, decreased proliferation, and increased cell death.
- Elevated inflammation and cell stress markers were observed in Dnm1l-/- NSCs.
Conclusions:
- Mitochondrial fission defects due to Dnm1l deficiency lead to compromised NSC self-renewal and premature aging.
- Dnm1l plays a critical role in maintaining NSC function and preventing age-related decline.
- Mitochondrial dysfunction is a key factor in the aging process of neural stem cells.

