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Updated: Dec 13, 2025
07:56
Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
Published on: November 30, 2022
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The mitophagy effector FUNDC1 controls mitochondrial reprogramming and cellular plasticity in cancer cells
Jie Li1,2, Ekta Agarwal1,2, Irene Bertolini1,2
1Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, PA 19104, USA.
Science Signaling
|July 30, 2020
Summary
Mitochondrial protein FUNDC1 regulates cancer cell plasticity by maintaining energy production and buffering ROS. Targeting FUNDC1 inhibits tumor growth but promotes cell invasion, revealing a new therapeutic strategy.
Area of Science:
- Cell Biology
- Mitochondrial Biology
- Cancer Research
Background:
- Mitochondria are crucial signaling hubs in eukaryotic cells.
- FUNDC1 (FUN14 domain-containing protein-1) is known for its role in Parkin-independent mitophagy.
- The broader functions of FUNDC1 in cellular processes remain to be fully elucidated.
Purpose of the Study:
- To investigate the role of FUNDC1 in cancer cell plasticity and bioenergetics.
- To identify FUNDC1 interacting partners and their functions.
- To understand the mechanism by which FUNDC1 influences tumor growth and invasion.
Main Methods:
- Utilized cancer cell models to study FUNDC1's function.
- Employed metabolomics and proteomics to identify FUNDC1 interactome.
- Assessed mitochondrial dynamics, ROS production, and cell proliferation/motility.
Main Results:
- FUNDC1 sustains oxidative bioenergetics, buffers ROS, and supports proliferation.
- Targeting FUNDC1 suppressed tumor growth but increased cell motility and invasion.
- Identified LonP1 and Complex V as key interactors of FUNDC1 at the mitochondrial inner membrane.
- FUNDC1-LonP1 axis maintains proteostasis, preserves Complex V function, and reduces ROS.
Conclusions:
- Mitochondrial reprogramming via the FUNDC1-LonP1 axis controls cancer cell plasticity.
- This axis switches cancer cells between proliferative and invasive states.
- Targeting this pathway offers a potential strategy for cancer therapy.
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