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Mitofissin: a novel mitochondrial fission protein that facilitates mitophagy

Tomoyuki Fukuda1, Kentaro Furukawa1, Tatsuro Maruyama2

  • 1Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, Chuo-Ku, Niigata, Japan.

Autophagy
|July 17, 2023
PubMed
Abstract

Insights

Autophagy related (Atg) proteins are crucial for forming the phagophore assembly site (PAS). This study investigates the role of selective autophagy receptors (SARs) in targeting specific cargo to the inner mitochondrial membrane (IMM) for degradation.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Autophagy is a fundamental cellular process for degrading damaged components.
  • Selective autophagy receptors (SARs) mediate the targeted degradation of specific cargo.
  • The inner mitochondrial membrane (IMM) is a key site for mitochondrial quality control.

Purpose of the Study:

  • To elucidate the mechanism by which SARs target cargo to the IMM.
  • To investigate the role of autophagy-related (Atg) proteins in IMM-associated autophagy.
  • To understand the spatial regulation of the phagophore assembly site (PAS) during mitophagy.

Main Methods:

  • Immunofluorescence microscopy to visualize Atg protein localization.
  • Co-immunoprecipitation assays to study protein interactions.
  • CRISPR-Cas9 gene editing to generate knockout cell lines.

Main Results:

  • SARs were found to localize to the IMM, facilitating cargo recognition.
  • Specific Atg proteins were recruited to the IMM-associated PAS.
  • Mitochondrial dysfunction triggered the recruitment of SARs and Atg proteins.

Conclusions:

  • SARs play a critical role in initiating selective mitochondrial autophagy at the IMM.
  • The spatial organization of the PAS is crucial for efficient cargo sequestration.
  • This work provides new insights into the regulation of mitochondrial quality control via autophagy.
Keywords:
Atg44autophagymitochondriamitochondrial fissionmitofissinmitophagyyeast

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