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A New Vision of Mitochondrial Unfolded Protein Response to the Sirtuin Family

Huidan Weng1,2,3, Yihong Ma4, Lina Chen1,2

  • 1Department of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian, 350001, China

Current Neuropharmacology
|January 25, 2020
PubMed

Insights

Mitochondrial damage triggers the mitochondrial unfolded protein response (mtUPR) to repair proteins. Sirtuins (SIRT1, SIRT3, SIRT7) are key regulators of this protective response in various diseases.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Biochemistry

Background:

  • Mitochondrial damage contributes to diseases like cancer and neurodegeneration.
  • The mitochondrial unfolded protein response (mtUPR) is a critical cellular defense against mitochondrial stress.
  • Sirtuins are crucial enzymes involved in cellular stress responses and metabolism.

Purpose of the Study:

  • To review the role of sirtuins in the mitochondrial unfolded protein response (mtUPR).
  • To explore molecular targets of sirtuins within the mtUPR.
  • To connect sirtuin-mtUPR pathways to disease pathogenesis and potential therapies.

Main Methods:

  • Literature review and synthesis of existing research.
  • Analysis of studies investigating sirtuin family members (SIRT1, SIRT3, SIRT7) and their roles in mtUPR.
  • Examination of molecular mechanisms and disease models.

Main Results:

  • Sirtuins, particularly SIRT1, SIRT3, and SIRT7, are integral components of the mtUPR.
  • These sirtuins modulate protein folding, degradation, and mitochondrial homeostasis.
  • Dysregulation of sirtuin-mediated mtUPR is implicated in neurodegenerative diseases and cancer.

Conclusions:

  • Sirtuins are essential regulators of the mitochondrial unfolded protein response.
  • Targeting sirtuin-mtUPR pathways offers therapeutic potential for mitochondrial dysfunction and related diseases.
  • Further research into sirtuins and mtUPR can advance understanding of mitochondrial health.
Keywords:
AMPKCHOPFOXO3APARPSIRTmitochondrial protein quality controlmitochondrial stressmitochondrial unfolded protein response

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