GO:0043653 mitochondrial fragmentation involved in apoptotic process: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0043653 describes the morphological shift of mitochondria from a branched network to fragmented vesicles during apoptosis.
• Mitochondrial fragmentation is a hallmark of intrinsic apoptosis and is often required for efficient cytochrome c release and caspase activation.
• Key regulators include dynamin-related protein 1 (DRP1), which is recruited to mitochondria and drives fission, as well as pro-apoptotic BCL-2 family proteins.
• The process is implicated in heart failure, skeletal muscle atrophy, and viral infections such as HIV-1.
• Experimental models include knockout of fission/fusion genes, point mutations in DRP1, and live-cell imaging of mitochondrial morphology.
• EDITGENE provides CRISPR services to dissect the genetic control of mitochondrial fragmentation in apoptosis.
Description
Mitochondrial fragmentation involved in apoptotic process (GO:0043653) is a biological process defined as the change in mitochondrial morphology from a highly branched network to a fragmented vesicular form during apoptosis. This process is distinct from physiological mitochondrial dynamics and is tightly linked to the execution of cell death. In apoptotic cells, the mitochondrial network undergoes rapid fission, resulting in numerous small, punctate mitochondria that facilitate the release of pro-apoptotic factors such as cytochrome c. The term captures a critical step that bridges mitochondrial dynamics and programmed cell death, and it is conserved across metazoans. Researchers study GO:0043653 because it represents a point of convergence for multiple death signals, including intrinsic apoptosis, viral infection, and tissue remodeling. The morphological transition is not merely a passive consequence of cell death but an actively regulated process involving fission machinery and BCL-2 family proteins. Understanding the molecular players and their regulation can reveal therapeutic targets for diseases characterized by excessive or insufficient apoptosis, such as heart failure, neurodegeneration, and cancer. This article synthesizes authoritative QuickGO data and verified PubMed literature to provide a research-grade overview of GO:0043653, covering its definition, mechanism, key genes, disease relevance, and experimental approaches. It is intended for scientists seeking to interrogate mitochondrial fragmentation in apoptotic contexts using CRISPR-based models and advanced imaging.
mitochondrial fragmentation involved in apoptotic process At A Glance
| GO ID | GO:0043653 |
|---|---|
| GO term | mitochondrial fragmentation involved in apoptotic process |
| Ontology | biological_process |
| Synonym | mitochondrial fission during apoptosis; mitochondrial fragmentation involved in apoptosis |
| Major function | Morphological transition of mitochondria from branched network to fragmented vesicles during apoptosis |
| Related processes | Apoptotic signaling, mitochondrial dynamics, cytochrome c release |
| Cellular location | Mitochondria |
| Key regulators | DRP1, BAX, BAK, and other BCL-2 family proteins |
What Is GO:0043653?
GO:0043653, mitochondrial fragmentation involved in apoptotic process, is defined by QuickGO as the change in the morphology of the mitochondria in an apoptotic cell from a highly branched network to a fragmented vesicular form. This process is also known as mitochondrial fission during apoptosis or mitochondrial fragmentation involved in apoptosis. It is a biological process that occurs specifically during apoptosis and is distinct from mitochondrial dynamics in healthy cells.
Why Is mitochondrial fragmentation involved in apoptotic process Important in Cell Biology?
Mitochondrial fragmentation involved in apoptotic process is important because it is a central event in the intrinsic apoptotic pathway, facilitating the release of cytochrome c and other pro-apoptotic factors that activate caspases. This process is conserved and is observed in diverse physiological and pathological contexts, including tissue remodeling, heart failure, skeletal muscle atrophy, and viral infections. Dysregulation of mitochondrial fragmentation contributes to diseases such as cancer, where evasion of apoptosis is a hallmark, and neurodegenerative disorders, where excessive cell death occurs. Therefore, understanding GO:0043653 provides mechanistic insights into cell death regulation and offers potential targets for therapeutic intervention.
• Essential for efficient cytochrome c release and apoptosome formation during intrinsic apoptosis.
• Involved in skeletal muscle atrophy and remodeling during myogenesis.
• Implicated in heart failure and cardiac dysfunction.
• Triggered by viral infections such as HIV-1 through protease-induced apoptosis.
• Regulated by BCL-2 family proteins and dynamin-related protein 1 (DRP1).
• Represents a potential therapeutic target for diseases with aberrant apoptosis.
• Can be studied using live-cell imaging and genetic perturbations.
• Links mitochondrial dynamics to cell cycle and cell death decisions.
• Provides a readout for mitochondrial health and apoptotic commitment.
• Offers a model to study organelle remodeling during cell death.
What Happens During mitochondrial fragmentation involved in apoptotic process?
Initiation by apoptotic signals
In simple terms: When a cell receives a death signal, mitochondria begin to change shape.
Apoptotic stimuli, such as DNA damage or growth factor withdrawal, activate pro-apoptotic BCL-2 family proteins like BAX and BAK, which translocate to mitochondria and initiate the intrinsic apoptotic pathway. This activation is a prerequisite for mitochondrial fragmentation, as it triggers downstream events that alter mitochondrial dynamics.
Recruitment of DRP1 to mitochondria
In simple terms: A protein called DRP1 moves to mitochondria and starts cutting them into pieces.
Dynamin-related protein 1 (DRP1) is a large GTPase that is recruited from the cytosol to the mitochondrial outer membrane during apoptosis. Its recruitment is mediated by adaptor proteins and is essential for the fission process. Once at the mitochondria, DRP1 oligomerizes and constricts the organelle in a GTP-dependent manner, leading to membrane scission.
Morphological transition to fragmented vesicles
In simple terms: The long, connected mitochondria break apart into many small, round pieces.
Following DRP1-mediated fission, the mitochondrial network disintegrates into numerous vesicular fragments. This morphological change is visible by microscopy and is a hallmark of apoptosis. The fragmented mitochondria are often referred to as 'punctate' and are distributed throughout the cytoplasm.
Facilitation of cytochrome c release
In simple terms: The broken mitochondria leak a protein that tells the cell to die.
Mitochondrial fragmentation promotes the release of cytochrome c from the intermembrane space into the cytosol. This release is a critical step in apoptosome formation and caspase activation. The fragmented state may increase the surface area or alter membrane curvature, facilitating the permeabilization of the outer membrane.
Regulation by fusion proteins
In simple terms: Proteins that normally fuse mitochondria are shut down to allow fragmentation.
During apoptosis, the fusion machinery, including mitofusins (MFN1/2) and OPA1, is often inhibited or degraded, tipping the balance toward fission. This downregulation of fusion proteins ensures that the fragmented state is maintained and that the apoptotic program proceeds efficiently.
Key Genes Involved in GO:0043653 mitochondrial fragmentation involved in apoptotic process
The following genes and proteins are central to mitochondrial fragmentation involved in apoptotic process, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| DRP1 (DNM1L) | GTPase that mediates mitochondrial fission | Key executor of fragmentation; knockout or dominant-negative mutants block fragmentation |
| BAX | Pro-apoptotic BCL-2 family protein; promotes mitochondrial outer membrane permeabilization | Activates fragmentation and cytochrome c release; knockout delays apoptosis |
| BAK | Pro-apoptotic BCL-2 family protein; cooperates with BAX | Essential for mitochondrial fragmentation in some cell types |
| MFN1 | Mitofusin; mediates outer membrane fusion | Inhibition or degradation promotes fragmentation |
| MFN2 | Mitofusin; mediates outer membrane fusion | Downregulation correlates with fragmentation during apoptosis |
| OPA1 | Inner membrane fusion protein | Proteolytic cleavage during apoptosis contributes to fragmentation |
| DAP3 | Death-associated protein 3; localizes to mitochondria | Involved in mitochondrial fragmentation during cell death |
| CYCS | Cytochrome c; released from fragmented mitochondria | Marker of apoptosis; release is facilitated by fragmentation |
| CASP3 | Executioner caspase | Activated downstream of cytochrome c release |
| CASP9 | Initiator caspase in apoptosome | Activated by cytochrome c; drives downstream events |
| APAF1 | Apoptosome component | Forms apoptosome with cytochrome c and caspase-9 |
| BCL2 | Anti-apoptotic BCL-2 family protein | Inhibits BAX/BAK and prevents fragmentation |
| BCL2L1 (BCL-XL) | Anti-apoptotic BCL-2 family protein | Blocks mitochondrial fragmentation |
| MFF | Mitochondrial fission factor; DRP1 receptor | Recruits DRP1 to mitochondria; knockdown reduces fragmentation |
| FIS1 | Mitochondrial fission protein; DRP1 receptor | Facilitates DRP1 recruitment; overexpression induces fragmentation |
| MIEF1 (MID51) | Mitochondrial elongation factor; regulates DRP1 | Modulates fission/fusion balance |
| MIEF2 (MID49) | Mitochondrial elongation factor; regulates DRP1 | Modulates fission/fusion balance |
| INF2 | Formin; promotes actin polymerization at mitochondria | Facilitates DRP1-mediated fission |
How Is mitochondrial fragmentation involved in apoptotic process Regulated?
Mitochondrial fragmentation involved in apoptotic process is regulated by a balance between fission and fusion machinery, as well as by BCL-2 family proteins. Pro-apoptotic BCL-2 proteins such as BAX and BAK promote fragmentation, while anti-apoptotic proteins like BCL-2 and BCL-XL inhibit it. Post-translational modifications of DRP1, including phosphorylation by cyclin-dependent kinase 1 (CDK1) and other kinases, modulate its activity and localization during apoptosis. Additionally, calcium signaling and reactive oxygen species can influence fragmentation. The process is also linked to cell cycle regulation, with fragmentation observed during mitosis in some contexts.
mitochondrial fragmentation involved in apoptotic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| DRP1 (DNM1L) | Heart failure, cancer | Knockout or point mutation in cardiomyocytes or cancer cell lines |
| BAX | Cancer, neurodegeneration | Knockout mice or cell lines to study apoptosis resistance |
| MFN2 | Charcot-Marie-Tooth disease type 2A | Knock-in of patient mutations in neuronal cells |
| DAP3 | Cancer, mitochondrial disorders | Overexpression or knockout in HeLa cells |
| OPA1 | Autosomal dominant optic atrophy | Knockout or point mutation in retinal ganglion cells |
Heart failure
Mitochondrial fragmentation is implicated in the pathogenesis of heart failure, where altered mitochondrial dynamics contribute to cardiomyocyte death and contractile dysfunction. In heart failure models, increased fission and decreased fusion are observed, and inhibition of DRP1 can be protective.
Skeletal muscle atrophy
During skeletal muscle atrophy, mitochondrial fragmentation is involved in remodeling and loss of muscle mass. Apoptotic signaling and mitochondrial dynamics are coordinated to remove damaged mitochondria and promote atrophy.
HIV-1 infection
HIV-1 protease can induce apoptosis and mitochondrial fragmentation in infected cells, contributing to CD4+ T cell depletion. This process involves the activation of intrinsic apoptosis and may be a target for therapeutic intervention.
Cancer
Cancer cells often evade apoptosis, and dysregulation of mitochondrial fragmentation can contribute to chemoresistance. Targeting the fission machinery, such as DRP1, is being explored as a strategy to sensitize cancer cells to apoptosis.
From mitochondrial fragmentation involved in apoptotic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate mitochondrial fragmentation during apoptosis? | CRISPR knockout of gene X in HeLa or HEK293T cells followed by live-cell imaging |
| Does a specific point mutation in DRP1 affect fission activity? | CRISPR point mutation knock-in of DRP1 variants in U2OS cells |
| Can a tagged version of DRP1 be used to track its localization? | CRISPR knock-in of fluorescent tag (e.g., GFP) at DRP1 locus |
| Does overexpression of BCL-2 block fragmentation? | Overexpression of BCL-2 in cancer cell lines |
| What is the role of DAP3 in mitochondrial fragmentation? | Knockout or overexpression of DAP3 in HeLa cells |
| Can CRISPR library screening identify novel regulators of fragmentation? | Genome-wide CRISPR knockout library in a reporter cell line |
How to Study the mitochondrial fragmentation involved in apoptotic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Real-time changes in mitochondrial morphology | Monitoring fragmentation during apoptosis |
| Immunofluorescence | Localization of DRP1, cytochrome c, etc. | Fixed-cell analysis of fragmentation |
| Western blot | Protein cleavage and expression levels | Detecting OPA1 processing and caspase activation |
| CRISPR knockout screen | Genes required for fragmentation | Unbiased discovery of regulators |
| Proteomics | Protein interactions and modifications | Identifying DRP1 interactors |
| RNA-seq | Transcriptional changes during apoptosis | Global gene expression analysis |
| Electron microscopy | Ultrastructure of fragmented mitochondria | High-resolution morphology |
| Flow cytometry | Mitochondrial membrane potential and mass | Quantifying apoptotic cells |
Live-cell imaging
Live-cell fluorescence microscopy using mitochondrial-targeted dyes or fluorescent proteins (e.g., MitoTracker, mito-GFP) allows real-time visualization of mitochondrial morphology changes during apoptosis. Time-lapse imaging can capture the transition from branched to fragmented networks.
Immunofluorescence and confocal microscopy
Fixed-cell immunofluorescence with antibodies against DRP1, cytochrome c, and other markers can reveal the localization and co-localization of proteins during fragmentation. Confocal microscopy provides high-resolution images of mitochondrial networks.
Western blotting
Western blot analysis can detect the cleavage of fusion proteins (e.g., OPA1, MFN1/2) and the activation of caspases during apoptosis. It also allows quantification of protein levels of key regulators.
CRISPR-based genetic screens
Genome-wide CRISPR knockout or activation screens coupled with a mitochondrial fragmentation reporter can identify novel genes that regulate this process. Such screens are powerful for unbiased discovery.
How CRISPR Can Be Used to Study GO:0043653 mitochondrial fragmentation involved in apoptotic process
Knockout
CRISPR knockout of genes such as DRP1, BAX, or BAK can be used to test their requirement for mitochondrial fragmentation during apoptosis. Knockout cell lines are generated by introducing indels in the target gene, leading to loss of protein expression. These models are valuable for epistasis experiments.
Point Mutation
CRISPR point mutation knock-in can introduce specific amino acid substitutions in genes like DRP1 to study their impact on GTPase activity and fission. For example, the K38A mutation in DRP1 acts as a dominant-negative and blocks fragmentation. Such models help dissect structure-function relationships.
Knock-in
CRISPR knock-in of fluorescent tags (e.g., GFP, mCherry) at endogenous loci allows real-time tracking of proteins like DRP1 or cytochrome c during apoptosis. Tagged knock-in models preserve endogenous regulation and are ideal for live-cell imaging.
Overexpression
CRISPR activation (CRISPRa) or traditional overexpression can be used to elevate levels of pro- or anti-apoptotic proteins to study their effects on mitochondrial fragmentation. Overexpression of BCL-2, for instance, blocks fragmentation and apoptosis.
How EDITGENE Supports mitochondrial fragmentation involved in apoptotic process Research
Researchers studying mitochondrial fragmentation involved in apoptotic process-related genes often need to determine whether a candidate gene is causally involved in the morphological transition or is merely a bystander. This requires precise genetic manipulation, which can be achieved through CRISPR-based knockout, point mutation, knock-in, or overexpression models. EDITGENE provides a comprehensive suite of services to support such investigations.
Contact EDITGENE today to design your custom CRISPR model for mitochondrial fragmentation involved in apoptotic process research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ERBB4 Knockout HEK293 Cell Line | EDJ-KQ655 | Human | 2066 | Details Get a Quote |
| BNIP3 Knockout HEK293 Cell Line | EDJ-KQ1023 | Human | 664 | Details Get a Quote |
| BAX Knockout HEK293 Cell Line | EDJ-KQ1747 | Human | 581 | Details Get a Quote |
| PRKN Knockout HEK293 Cell Line | EDJ-KQ3360 | Human | 5071 | Details Get a Quote |
| FIS1 Knockout HEK293 Cell Line | EDJ-KQ10875 | Human | 51024 | Details Get a Quote |
| CCAR2 Knockout HEK293 Cell Line | EDJ-KQ11949 | Human | 57805 | Details Get a Quote |
| ATG3 Knockout HEK293 Cell Line | EDJ-KQ12466 | Human | 64422 | Details Get a Quote |
| BNIP3L Knockout HEK293 Cell Line | EDJ-KQ12552 | Human | 665 | Details Get a Quote |
| VPS35 Knockout HEK293 Cell Line | EDJ-KQ16107 | Human | 55737 | Details Get a Quote |
| BNIP3L Knockout HeLa Cell Line | EDJ-KQ18103 | Human | 665 | Details Get a Quote |
| ERBB4 Knockout HeLa Cell Line | EDJ-KQ19161 | Human | 2066 | Details Get a Quote |
| BNIP3 Knockout A-549 Cell Line | EDJ-KQ20110 | Human | 664 | Details Get a Quote |
| BNIP3 Knockout HCT 116 Cell Line | EDJ-KQ20111 | Human | 664 | Details Get a Quote |
| ATG3 Knockout A-549 Cell Line | EDJ-KQ41409 | Human | 64422 | Details Get a Quote |
| ATG3 Knockout HCT 116 Cell Line | EDJ-KQ41410 | Human | 64422 | Details Get a Quote |
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Frequently Asked Questions About mitochondrial fragmentation involved in apoptotic process
What is GO:0043653?
GO:0043653 is the Gene Ontology term for mitochondrial fragmentation involved in apoptotic process, defined as the change in mitochondrial morphology from a branched network to fragmented vesicles during apoptosis.
What genes are involved in mitochondrial fragmentation during apoptosis?
Key genes include DRP1 (DNM1L), BAX, BAK, MFN1, MFN2, OPA1, and DAP3, among others.
How is mitochondrial fragmentation regulated?
It is regulated by the balance between fission and fusion proteins, BCL-2 family proteins, and post-translational modifications of DRP1.
Why is mitochondrial fragmentation important in apoptosis?
It facilitates cytochrome c release and caspase activation, which are essential for the execution of apoptosis.
What diseases are associated with mitochondrial fragmentation?
Heart failure, skeletal muscle atrophy, HIV-1 infection, cancer, and neurodegenerative disorders.
How can I study mitochondrial fragmentation in the lab?
Common methods include live-cell imaging, immunofluorescence, Western blotting, and CRISPR-based genetic screens.
What is the role of DRP1 in mitochondrial fragmentation?
DRP1 is a GTPase that mediates mitochondrial fission; its recruitment to mitochondria is a key step in fragmentation during apoptosis.
Can CRISPR be used to study mitochondrial fragmentation?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are widely used to dissect the genetic control of this process.
What is the difference between mitochondrial fragmentation and fusion?
Fragmentation is the fission of mitochondria into smaller units, while fusion is the joining of mitochondria; both are regulated by distinct protein machineries.
Where can I find validated CRISPR models for mitochondrial fragmentation research?
EDITGENE provides custom CRISPR services including knockout, point mutation, knock-in, overexpression, and library screening for genes involved in mitochondrial fragmentation.
Conclusion
Mitochondrial fragmentation involved in apoptotic process (GO:0043653) is a critical morphological event in intrinsic apoptosis, driven by the fission machinery and regulated by BCL-2 family proteins. Its dysregulation is linked to heart failure, muscle atrophy, viral infections, and cancer. Understanding the molecular players and their regulation offers opportunities for therapeutic intervention. EDITGENE's CRISPR services provide powerful tools to investigate this process and identify novel targets.
References
- 1. Arnoult D. 2007. Mitochondrial fragmentation in apoptosis.. Trends Cell Biol 17(1):6-12 PMID: 17116393
- 2. Rahman FA et al.. 2023. Mitochondrial Apoptotic Signaling Involvement in Remodeling During Myogenesis and Skeletal Muscle Atrophy.. Semin Cell Dev Biol 143:66-74 PMID: 35241367
- 3. Mukamel Z et al.. 2004. Death-associated protein 3 localizes to the mitochondria and is involved in the process of mitochondrial fragmentation during cell death.. J Biol Chem 279(35):36732-8 PMID: 15175341
- 4. Knowlton AA et al.. 2015. Mitochondrial Dynamics and Heart Failure.. Compr Physiol 6(1):507-26 PMID: 26756641
- 5. Hohorst L et al.. 2025. Mitochondrial dynamics and pore formation in regulated cell death pathways.. Trends Biochem Sci 50(11):1001-1014 PMID: 41044022
- 6. Rumlová M et al.. 2014. HIV-1 protease-induced apoptosis.. Retrovirology 11:37 PMID: 24886575
- 7. Cosentino K et al.. 2014. Mitochondrial alterations in apoptosis.. Chem Phys Lipids 181:62-75 PMID: 24732580
- 8. Horbay R et al.. 2016. Mitochondrial dynamics during cell cycling.. Apoptosis 21(12):1327-1335 PMID: 27658785
