Improvement of cognitive and motor performance with mitotherapy in aged mice

Zhao, Zizhen; Yu, Zhenyao; Hou, Yixue; Le, Zhang; Fu, Ailing

doi:10.7150/ijbs.40886

Cited by 39 publications

(27 citation statements)

References 32 publications

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“…26 These advantageous ability of the mitochondria has been utilized in the treatment of mitochondria-related diseases, including myocardial ischemia, cerebral ischemia, schizophrenia, depression, aging, and tumor. 21,27 In the study, the elevated serum transaminase activities, and the decreased GSH and SOD levels that is intoxicated with CCl4, were predominately stopped by the exogenous mitochondrial administration. Also, the mitochondria prevented liver fibrosis and retained the ultracellular structure of the hepatocytes.…”

Section: Discussionmentioning

confidence: 95%

“…However, only ATP administration does not show improvement in cardiac function, which implies that mitochondrial therapy could induce tissue regeneration 26 . This advantageous ability of the mitochondria has been utilized in the treatment of mitochondria‐related diseases, including myocardial ischemia, cerebral ischemia, schizophrenia, depression, aging, and tumor 21,27 . In the study, the elevated serum transaminase activities, and the decreased GSH and SOD levels that is intoxicated with CCl 4, were predominately stopped by the exogenous mitochondrial administration.…”

Section: Discussionmentioning

confidence: 98%

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Mitochondrial transplantation therapy inhibit carbon tetrachloride‐induced liver injury through scavenging free radicals and protecting hepatocytes

Zhao

Hou

Zhou

et al. 2020

Bioengineering & Transla Med

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Carbon tetrachloride (CCl4)‐induced liver injury is predominantly caused by free radicals, in which mitochondrial function of hepatocytes is impaired, accompanying with the production of ROS and decreased ATP energy supply in animals intoxicated with CCl4. Here we explored a novel therapeutic approach, mitochondrial transplantation therapy, for treating the liver injury. The results showed that mitochondria entered hepatocytes through macropinocytosis pathway, and thereby cell viability was recovered in a concentration‐dependent manner. Mitochondrial therapy could increase ATP supply and reduce free radical damage. In liver injury model of mice, mitochondrial therapy significantly improved liver function and prevented tissue fibrogenesis. Transcriptomic data revealed that mitochondrial unfold protein response (UPRmt), a protective transcriptional response of mitochondria‐to‐nuclear retrograde signaling, would be triggered after mitochondrial administration. Then the anti‐oxidant genes were up‐regulated to scavenge free radicals. The mitochondrial function was rehabilitated through the transcriptional activation of respiratory chain enzyme and mitophage‐associated genes. The protective response re‐balanced the cellular homeostasis, and eventually enhanced stress resistance that is linked to cell survival. The efficacy of mitochondrial transplantation therapy in the animals would suggest a novel approach for treating liver injury caused by toxins.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 98%

Mitochondrial transplantation therapy inhibit carbon tetrachloride‐induced liver injury through scavenging free radicals and protecting hepatocytes

Zhao

Hou

Zhou

et al. 2020

Bioengineering & Transla Med

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“…4 ). Further, mitochondria in blood can activate immune system through increasing the activities of phagocytes and T cells 49 , 50 , which might increase the anti-tumor effect of the mitochondria to a certain extent. The mitochondria on tumor immunity will be further investigated.…”

Section: Discussionmentioning

confidence: 99%

The effect of mitochondrial transplantation therapy from different gender on inhibiting cell proliferation of malignant melanoma

Hou

Zhou

et al. 2021

Int. J. Biol. Sci.

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Today mitochondria are considered much more than a energy plant in cells. Mitochondrial transplantation therapy has been an active research area for treating mitochondria-associated diseases from animal studies to clinical trials. However, the specific mechanism involved in the anti-tumor activity of healthy mitochondria remain to be characterized. Here we investigate the signal mechanism and gender difference of mitochondrial transplantation therapy against malignant melanoma. In the study, we administrated intact mitochondria extracted from mouse livers respectively to the mice bearing malignantly subcutaneous and metastatic melanoma, and identified the signal mechanism responsible for the mitochondrial treatment through transcriptomic analysis. Meanwhile, the efficiency of female mitochondria and male mitochondria was compared in the cultured melanoma cells and transplanted melanoma in mice. The results suggested that the mitochondria significantly inhibited the tumor cell proliferation in vitro through cell cycle arrest and induction of cell apoptosis. In the melanoma-bearing mice, the mitochondria retard the tumor growth and lung migration, and the transcriptomic analysis indicated that general chromosome silencing was strongly associated with the mitochondria against melanoma after the mitochondrial transplantation on the metastasis melanoma. Moreover, the anti-tumor activity of mitochondria from female animals was more efficient in comparison to the males, and the female mitochondria could probably induce more persuasive mitochondria-nuclear communication than the mitochondria from male mice. The study identifies the anti-tumor mechanism of the mitochondrial transplantation therapy, and provides a novel insight into the effect of mitochondria from different gender.

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“…These data suggest that the transplantation of mitochondria led to antidepressant-like effects, modulated the brain immune response, mitochondria bioenergetics and adult hippocampal neurogenesis. The systemic administration of mitochondria also increased the forced swimming score and decreased latency on water maze tests in aged mice, although the treatment did not match the aging effects to young mouse scores [ 31 ].…”

Section: Mitotherapy In the Central Nervous Systemmentioning

confidence: 99%

Mitotherapy: Unraveling a Promising Treatment for Disorders of the Central Nervous System and Other Systemic Conditions

Nascimento-dos-Santos

de‐Souza‐Ferreira

Linden

et al. 2021

Cells

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Mitochondria are key players of aerobic respiration and the production of adenosine triphosphate and constitute the energetic core of eukaryotic cells. Furthermore, cells rely upon mitochondria homeostasis, the disruption of which is reported in pathological processes such as liver hepatotoxicity, cancer, muscular dystrophy, chronic inflammation, as well as in neurological conditions including Alzheimer’s disease, schizophrenia, depression, ischemia and glaucoma. In addition to the well-known spontaneous cell-to-cell transfer of mitochondria, a therapeutic potential of the transplant of isolated, metabolically active mitochondria has been demonstrated in several in vitro and in vivo experimental models of disease. This review explores the striking outcomes achieved by mitotherapy thus far, and the most relevant underlying data regarding isolated mitochondria transplantation, including mechanisms of mitochondria intake, the balance between administration and therapy effectiveness, the relevance of mitochondrial source and purity and the mechanisms by which mitotherapy is gaining ground as a promising therapeutic approach.

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Improvement of cognitive and motor performance with mitotherapy in aged mice

Cited by 39 publications

References 32 publications

Mitochondrial transplantation therapy inhibit carbon tetrachloride‐induced liver injury through scavenging free radicals and protecting hepatocytes

Mitochondrial transplantation therapy inhibit carbon tetrachloride‐induced liver injury through scavenging free radicals and protecting hepatocytes

The effect of mitochondrial transplantation therapy from different gender on inhibiting cell proliferation of malignant melanoma

Mitotherapy: Unraveling a Promising Treatment for Disorders of the Central Nervous System and Other Systemic Conditions

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