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Apoptosis-inducing factor starts its activity within mitochondria revealed by in situ vibrational probes

Jinyu Zhu1, Yi Liao2, Mengfan Feng1

  • 1State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, People's Republic of China.

Proceedings of the National Academy of Sciences of the United States of America
|May 20, 2026
PubMed

Insights

Apoptosis-inducing factor (AIF) and nicotinamide adenine dinucleotide (NADH) drive cell death by interacting within mitochondria. This study reveals their molecular mechanisms, offering potential cancer therapeutic strategies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Apoptosis-inducing factor (AIF) is a mitochondrial protein.
  • AIF is implicated in caspase-independent cell death.
  • Its precise role in apoptosis requires further elucidation.

Purpose of the Study:

  • To explore the proapoptotic activity of AIF within mitochondria.
  • To investigate the molecular mechanisms underlying AIF-mediated cell death.
  • To understand the interplay between AIF, cytochrome c, and NADH in apoptosis.

Main Methods:

  • Label-free vibrational spectroscopy and imaging.
  • Resonance Raman spectroscopy.
  • Molecular dynamics simulations.
  • In situ Raman probes.
  • Flow cytometry.

Main Results:

  • Electron transfer between AIF and cytochrome c (Cyt c) was observed.
  • NADH-AIF-dependent reactive oxygen species (ROS) generation and phospholipid peroxidation were elucidated.
  • AIF and Cyt c synergistically contribute to mitochondrial membrane permeabilization via a ROS-independent pathway.
  • NADH-dependent Cyt c release from mitochondria was monitored in real-time.
  • The proapoptotic role of NADH was confirmed.

Conclusions:

  • AIF and Cyt c have a synergistic role in mitochondrial membrane permeabilization.
  • NADH plays a crucial role in Cyt c release and apoptosis.
  • Understanding these mechanisms can inform cancer therapeutic strategies.
Keywords:
apoptosisapoptosis-inducing factorcytochrome celectron transferphospholipid peroxidation

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