Related Experiment Video

Updated: Mar 26, 2026

Assessment of Mitochondrial Fission/Fusion Dynamics in Kidney Proximal Tubular Cells
06:14

Assessment of Mitochondrial Fission/Fusion Dynamics in Kidney Proximal Tubular Cells

Published on: November 14, 2025

755

Appoptosin interacts with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology

Cuilin Zhang1, Zhun Shi1, Lingzhi Zhang1

  • 1Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Pharmaceutical Sciences, College of Medicine, Collaborative Innovation Center for Brain Science, Xiamen University, Xiamen, Fujian 361102, China.

Journal of Cell Science
|January 28, 2016
PubMed

Insights

Appoptosin, a mitochondrial protein, causes mitochondrial fragmentation and apoptosis by interacting with outer-membrane fusion proteins, independent of its carrier function. This finding offers new insights into mitochondrial dynamics and related diseases.

Area of Science:

  • Cell Biology
  • Mitochondrial Biology
  • Neuroscience

Background:

  • Mitochondrial morphology is crucial for cellular health and regulated by fusion and fission processes.
  • Dysfunctional mitochondrial dynamics are implicated in neurodegenerative diseases like Alzheimer's disease.
  • Appoptosin (SLC25A38) is a mitochondrial inner membrane protein linked to reactive oxygen species (ROS) production and apoptosis.

Purpose of the Study:

  • To investigate the role of appoptosin in regulating mitochondrial morphology and dynamics.
  • To elucidate the molecular mechanisms by which appoptosin influences mitochondrial fragmentation and apoptosis.
  • To determine if appoptosin's effects are dependent on its carrier function, ROS production, or caspase activation.

Main Methods:

  • Overexpression of appoptosin in cells.
  • Analysis of mitochondrial morphology and fragmentation.
  • Western blotting to assess levels of fusion and fission proteins (MFN1, MFN2, OPA1, DRP1, FIS1).
  • Co-immunoprecipitation to study protein interactions.
  • Rescue experiments using co-expression of specific proteins.

Main Results:

  • Appoptosin overexpression induced mitochondrial fragmentation independently of its carrier function, ROS, or caspase activation.
  • Appoptosin interacted with MFN1, MFN2, and MITOL, but not OPA1, FIS1, or DRP1.
  • Appoptosin impaired the interaction between MFN1 and MFN2, inhibiting mitochondrial fusion.
  • Co-expression of MFN1, MITOL, and dominant-negative DRP1 partially rescued fragmentation and apoptosis, while FIS1 aggravated apoptosis.

Conclusions:

  • Appoptosin regulates mitochondrial morphology by interacting with mitochondrial outer-membrane fusion proteins.
  • Appoptosin's role in mitochondrial fragmentation and apoptosis is mediated through modulation of MFN1/MFN2 interactions.
  • These findings highlight a novel mechanism by which appoptosin influences mitochondrial dynamics, relevant to Alzheimer's disease pathogenesis.
Keywords:
ApoptosisAppoptosinMFN1MFN2MITOLMitochondrial dynamics

More Related Videos

A Faster, High Resolution, mtPA-GFP-based Mitochondrial Fusion Assay Acquiring Kinetic Data of Multiple Cells in Parallel Using Confocal Microscopy10:45

A Faster, High Resolution, mtPA-GFP-based Mitochondrial Fusion Assay Acquiring Kinetic Data of Multiple Cells in Parallel Using Confocal Microscopy

Published on: July 20, 2012

17.3K
A Model Membrane Platform for Reconstituting Mitochondrial Membrane Dynamics10:31

A Model Membrane Platform for Reconstituting Mitochondrial Membrane Dynamics

Published on: September 2, 2020

8.2K

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...
9.2K
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
6.0K
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,...
13.7K
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
17.7K
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
3.9K
The Inner Mitochondrial Membrane01:28

The Inner Mitochondrial Membrane

The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria.  In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
5.0K