Pum2-Mff axis fine-tunes mitochondrial quality control in acute ischemic kidney injury

Area of Science:

• Mitochondrial biology
• Renal pathophysiology
• Molecular mechanisms of cell injury

Background:

• Mitochondrial fission factor (Mff) regulates mitochondrial quality control, including cleavage and cell death.
• RNA-binding protein Pumilio2 (Pum2) negatively regulates Mff mRNA translation.
• The interplay between Pum2 and Mff in acute kidney injury (AKI) remains underexplored.

Purpose of the Study:

• To investigate the roles of Pum2 and Mff in mitochondrial quality control during ischemic AKI in a murine model.
• To elucidate the molecular mechanisms underlying the Pum2-Mff axis in ischemic AKI.

Main Methods:

• Utilized a murine model of ischemic acute kidney injury (AKI).
• Investigated the effects of Mff genetic deletion and Pum2 overexpression on renal function and mitochondrial homeostasis.
• Employed Western blot analysis to assess protein levels of Pum2 and Mff.
• Evaluated inflammatory response, oxidative stress, tubular cell death, mitochondrial mitosis, Sirt1/3 expression, and mitochondrial respiration.

Main Results:

• Genetic deletion of Mff attenuated ischemic AKI-induced renal failure by inhibiting inflammation, oxidative stress, and cell death.
• Mff inhibition preserved mitochondrial homeostasis, improving mitochondrial mitosis, Sirt1/3 expression, and respiration.
• Ischemic AKI downregulated Pum2 while upregulating Mff; Pum2 overexpression counteracted Mff upregulation and protected renal tubules.
• The Pum2-Mff axis was identified as a key regulator of mitochondrial quality control in ischemic AKI.

Conclusions:

• The Pum2-Mff axis plays a critical role in regulating mitochondrial quality control during ischemic AKI.
• Mff inhibition and Pum2 activation demonstrate therapeutic potential for managing ischemic AKI.