Retrograde signaling is required for Slm35-mediated negative regulation of mitophagy in yeast

Hilario Ruelas-Ramírez1, Ariann E Mendoza-Martínez1, P Abril Medina-Flores1

  • 1Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Coyoacán, Mexico City 04510, Mexico.

Biology Open
|December 10, 2025
PubMed

Insights

Slm35 protein acts as a novel negative regulator of mitophagy, controlling mitochondrial quality. It fine-tunes the mitochondrial retrograde (RTG) signaling pathway, crucial for cellular health and metabolic homeostasis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitophagy is vital for mitochondrial quality control and cellular health.
  • Mechanisms downregulating mitophagy are less understood than those promoting it.

Purpose of the Study:

  • Investigate the role of Saccharomyces cerevisiae Slm35 in mitophagy regulation.
  • Identify Slm35 as a novel negative regulator of mitophagy and the mitochondrial retrograde (RTG) pathway.

Main Methods:

  • Characterized Slm35 as a soluble mitochondrial matrix protein.
  • Assessed Slm35's impact on mitophagy and RTG signaling pathway dynamics.

Main Results:

  • Slm35 negatively regulates mitophagy and the RTG pathway.
  • Slm35's regulation of mitophagy is independent of Atg32 processing and mitochondrial membrane potential.
  • Slm35 is essential for dynamic RTG pathway regulation during mitophagy induction.

Conclusions:

  • Slm35 is a key player in fine-tuning mitochondrial quality control.
  • Dynamic regulation of the RTG pathway by Slm35 is critical for controlling mitophagy.

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