4.6 Article

Mitochondrial Transfusion Improves Mitochondrial Function Through Up-regulation of Mitochondrial Complex II Protein Subunit SDHB in the Hippocampus of Aged Mice

期刊

MOLECULAR NEUROBIOLOGY
卷 59, 期 10, 页码 6009-6017

出版社

SPRINGER
DOI: 10.1007/s12035-022-02937-w

关键词

Mitochondrial dysfunction; Bioenergetics; Complex II; Aging; Age-related disease; Mitochondrial transfusion; Brain; Neuroscience

资金

  1. Mitrix Bio Company
  2. St. Boniface Hospital Research Foundation [1406-3216, 1410-3216]
  3. Canadian Institute of Health Research (CIHR) [PJT-162144]
  4. Alzheimer's Society of Manitoba
  5. Royal Canadian Properties Limited Endowment Fund [1403-3131]
  6. Alzheimer's Soc. of Manitoba
  7. Research Manitoba

向作者/读者索取更多资源

The mitochondrial theory of aging focuses on dysfunction of the mitochondrial electron transport chain, leading to the aging process; Studies have shown that mitochondrial transfusion can significantly improve mitochondrial function in elderly mice; Mitochondrial complex II may serve as a potential target for therapeutic interventions in aging.
The mitochondrial theory of aging is characterized by mitochondrial electron transport chain dysfunction. As a hallmark of aging, an increasing number of investigations have attempted to improve mitochondrial function in both aging and age-related disease. Emerging from these attempts, methods involving mitochondrial isolation, transfusion, and transplantation have taken center stage. In particular, mitochondrial transfusion refers to the administration of mitochondria from healthy tissue into the bloodstream or into tissues affected by injury, disease, or aging. In this study, methods of mitochondrial isolation and transfusion were developed and utilized. First, we found a significant decrease (p < 0.05) in the expression of mitochondrial complex proteins (I-V) in aged (12 months old) mouse brain tissue (C57BL/6 mice) in comparison to healthy young brain tissue (1 month old). To investigate whether healthy young mitochondria taken from the liver could improve mitochondrial function in older animals, we intravenously injected mitochondria isolated from young C57BL/6 mice into aged mice from the same strain. This study, for the first time, demonstrates that mitochondrial transfusion significantly (p < 0.05) improves mitochondrial function via the up-regulation of the mitochondrial complex II protein subunit SDHB in the hippocampus of aged mice. This result has identified a role for mitochondrial complex II in the aging process. Therefore, mitochondrial complex II could serve as a putative target for therapeutic interventions against aging. However, more importantly, methods of mitochondrial transfusion should be further tested to treat a variety of human diseases or disorders and to slow down or reverse processes of aging.

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