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mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases

Paula Cilleros-Holgado1, David Gómez-Fernández1, Rocío Piñero-Pérez1

  • 1Centro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), 41013 Sevilla, Spain.

International Journal of Molecular Sciences
|January 21, 2023
PubMed

Insights

Modulating the mitochondrial unfolded protein response (mtUPR) offers a promising therapeutic strategy for mitochondrial dysfunction, improving cell health in various diseases. However, caution is advised due to potential risks in cancer and side effects from overactivation.

Area of Science:

  • Mitochondrial Biology
  • Cellular Stress Responses
  • Therapeutic Strategies

Background:

  • Mitochondrial dysfunction is central to numerous diseases, impacting energy production, calcium balance, apoptosis, and reactive oxygen species (ROS).
  • Current treatments for primary and secondary mitochondrial diseases remain limited.
  • The mitochondrial unfolded protein response (mtUPR) represents a novel therapeutic avenue.

Purpose of the Study:

  • To review current data on mtUPR modulation as a therapeutic approach.
  • To explore the role of mtUPR in various diseases.
  • To discuss potential negative consequences of mtUPR activation.

Main Methods:

  • Review of recent scientific literature on mtUPR.
  • Analysis of mtUPR's role in cellular homeostasis and disease models.
  • Evaluation of therapeutic potential and risks associated with mtUPR modulation.

Main Results:

  • mtUPR activation promotes cell homeostasis and improves outcomes in models of mitochondrial dysfunction, age-related diseases, cardiopathies, metabolic disorders, and primary mitochondrial diseases.
  • mtUPR activation may paradoxically promote tumor progression in cancer.
  • Overactivation of mtUPR can lead to adverse effects, including increased mitochondrial DNA (mtDNA) heteroplasmy.

Conclusions:

  • mtUPR modulation is a promising therapeutic strategy for mitochondrial dysfunction-related conditions.
  • Careful consideration of mtUPR's dual role in disease and potential side effects is crucial for its clinical application.
  • Further research is needed to optimize mtUPR-based therapies and mitigate risks.
Keywords:
ageingcancercardiovascular diseasesmetabolic diseasesmitochondriamitochondrial biogenesismitochondrial diseasesmitochondrial unfolded protein responseneurodegenerative diseasesproteostasistherapeutic target

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