Related Experiment Video
Updated: Jun 2, 2025
07:40
Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy
Published on: May 26, 2023
1.1K
ZFAND6 promotes TRAF2-dependent mitophagy to restrain cGAS-STING signaling
Kashif Shaikh1, Melissa Bowman2, Sarah M McCormick2
1Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA 17033, USA.
Iscience
|January 15, 2025
Summary
ZFAND6 protein maintains mitochondrial health by promoting mitophagy, clearing damaged mitochondria. Its absence increases ROS and triggers immune responses, enhancing viral resistance.
Area of Science:
- Cellular Biology
- Immunology
- Mitochondrial Biology
Background:
- ZFAND6 (Zinc Finger And NUMB Like 6) is a protein involved in tumor necrosis factor (TNF) signaling.
- It interacts with TNF receptor-associated factor 2 (TRAF2) and polyubiquitin chains.
Purpose of the Study:
- To investigate the previously undescribed function of ZFAND6 in maintaining mitochondrial homeostasis.
- To elucidate the mechanism by which ZFAND6 regulates mitophagy and its impact on cellular responses.
Main Methods:
- Deletion of ZFAND6 in bone marrow-derived macrophages (BMDMs).
- Assessment of reactive oxygen species (ROS) levels and mitochondrial accumulation.
- Analysis of mitochondrial DNA (mtDNA) release and interferon-stimulated gene (ISG) expression.
- Investigation of the role of stimulator of interferon genes (STING) pathway.
- Examination of ZFAND6's interaction with TRAF2 and cIAP1.
Main Results:
- ZFAND6 deletion in BMDMs led to increased ROS and damaged mitochondria due to impaired mitophagy.
- Mitochondrial DNA release into the cytoplasm triggered STING-dependent ISG expression.
- This resulted in enhanced resistance to viral infections.
- ZFAND6 was found to bridge TRAF2-cIAP1 interactions and recruit TRAF2 to damaged mitochondria, initiating mitophagy.
Conclusions:
- ZFAND6 plays a crucial role in maintaining mitochondrial homeostasis by promoting mitophagy.
- The protein facilitates the clearance of damaged mitochondria through a TRAF2-cIAP1-dependent mechanism.
- ZFAND6-mediated mitophagy influences innate immune responses and viral resistance.
Related Concept Videos
01:07MAPK Signaling Cascades
5.1K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.1K
01:22Amplifying Signals via Enzymatic Cascade
8.3K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.3K
01:19Interactions Between Signaling Pathways
6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
01:16TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
03:03mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K
01:15Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K