Related Experiment Video

Updated: Apr 25, 2026

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
07:56

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome

Published on: November 30, 2022

6.0K

The BCL2L1 and PGAM5 axis defines hypoxia-induced receptor-mediated mitophagy

Hao Wu1, Danfeng Xue2, Guo Chen3

  • 1State Key Laboratory of Biomembrane and Membrane Biotechnology; Institute of Zoology; Chinese Academy of Sciences; Beijing, China; University of Chinese Academy of Sciences; Beijing, China.

Autophagy
|August 16, 2014
PubMed

Insights

Bcl-xL (BCL2L1) protein suppresses mitophagy, a cellular process for removing damaged mitochondria, by inhibiting the PGAM5 phosphatase. This prevents FUNDC1 dephosphorylation, crucial for hypoxia-induced mitophagy.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Mitochondrial Dynamics

Background:

  • Receptor-mediated mitophagy is vital for mitochondrial quality control and cell survival.
  • FUNDC1 was previously identified as a key mitophagy receptor in mammals.
  • Regulation of mitophagy by cellular cues remains incompletely understood.

Purpose of the Study:

  • To investigate the regulatory mechanisms of receptor-mediated mitophagy.
  • To identify proteins that modulate FUNDC1-mediated mitophagy.
  • To elucidate the role of BCL2 family proteins in mitophagy.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • In vitro phosphatase assays to assess enzyme activity.
  • Western blotting to detect protein phosphorylation status.
  • Cellular mitophagy assays under hypoxic conditions.

Main Results:

  • BCL2L1 (Bcl-xL), but not BCL2, was found to suppress FUNDC1-mediated mitophagy via its BH3 domain.
  • BCL2L1 directly interacts with and inhibits the mitochondrial phosphatase PGAM5.
  • Inhibition of PGAM5 by BCL2L1 prevents FUNDC1 dephosphorylation at Ser13, a key step for mitophagy activation.
  • The BCL2L1-PGAM5-FUNDC1 pathway is essential for hypoxia-induced mitophagy.

Conclusions:

  • BCL2L1 plays a unique and inhibitory role in FUNDC1-mediated mitophagy, distinct from BCL2.
  • The BCL2L1-PGAM5-FUNDC1 axis is a critical regulatory pathway for mitophagy in response to hypoxia.
  • Understanding this pathway offers insights into mitochondrial quality control mechanisms.
Keywords:
BCL2L1/Bcl-xLFUNDC1PGAM5 phosphatasehypoxiamitophagy

More Related Videos

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice08:40

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice

Published on: November 22, 2017

17.2K
Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima09:13

Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima

Published on: August 12, 2018

14.7K

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
8.8K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.1K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.3K
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
71