Reagent Selection Guide for Cancer, Neurodegeneration, and Senescence Research DOJINDO LABORATORIES

Overview

Cancer, neurodegeneration and senescence are major areas of contemporary medical research. The pathological mechanisms underlying these conditions involve a complex interplay of interrelated cellular phenomena, such as cell death and the cellular senescence pathway. These phenomena are often centered on mitochondrial function, highlighting the central role of mitochondria in the pathogenesis of cancer¹⁾, neurodegeneration and senescence²⁾, while also highlighting promising therapeutic targets for these disorders.

Related Products

① Protective Pathway

Autophagy

First-time autophagy research
・Autophagic Flux Assay Kit

Autophagy (Autolysosome) Detection
・DALGreen - Autophagy Detection

Autophagy (Autophagosome) Detection
・DAPGreen - Autophagy Detection

Autophagy (Autophagosome) Detection
・DAPRed - Autophagy Detection

Mitophagy

Mitophagy Detection
・Mitophagy Detection Kit

Lysosome

Lysosomal function
・Lysosomal Acidic pH Detection Kit -Green/Red and Green/Deep Red

Lysosomal pH Detection
・pHLys Red- Lysosomal Acidic pH Detection

Lysosomal mass detection
・LysoPrime Green- High Specificity and pH Resistance and Deep Red

② Mitochondrial
function indicators

Mitochondrial dysfunction

Mitochondrial membrane potential detection
・JC-1 MitoMP Detection Kit
・MT-1 MitoMP Detection Kit

ROS Detection
・ROS Assay Kit -Highly Sensitive DCFH-DA-
・ROS Assay Kit -Photo-oxidation Resistant DCFH-DA-

Mitochondrial superoxide detection
・MitoBright ROS - Mitochondrial Superoxide Detection

Metabolic shift

Glycolysis/Oxidative phosphorylation assay
・Glycolysis/OXPHOS Assay Kit

Oxygen consumption rate assay
・Extracellular OCR Plate Assay Kit
・Intracellular Oxygen Assay Kit

③ Detectors

Cell Cytotoxicity

Cellular dehydrogenase activity
・CCK-8 (Cell Counting Kit-8)

Released Lacate dehydrogenase (LDH)
・Cytotoxicity LDH Assay Kit-WST

Apoptosis

Apoptosis detection (For plate reader)
・Annexin V Apoptosis Plate Assay Kit

ADP/ATP Ratio
・ADP/ATP Ratio Assay Kit-Luminescence

Ferroptosis

Intracellular ferrous ion (Fe²⁺) detection
・FerroOrange

Mitochondrial ferrous ion (Fe²⁺) detection
・MitoFerro-Green

Lipid peroxidation detection (Intracellular)
・Liperfluo
・Lipid Peroxidation Probe -BDP 581/591 C11-
・MDA Assay Kit

Lipid peroxidation detection (Mitochondrial)
MitoPeDPP

Senecence

SA-βGal detection
・SPiDER-βGal for live-cell imaging or flow cytometry
・SPiDER-βGal Blue for fixed cell and for multiple staining with immunostaining and other methods
・SPiDER-βGal for microplate reader
・SPiDER-βGal for tissue samples

Change of cell cycle
・Cell Cycle Assay Solution Deep Red
・Cell Cycle Assay Solution Blue

Nucleolar staining
・Nucleolus Bright Green
・Nucleolus Bright Red

Click to learn additional information about the relationship between mitochondria and,

Cancer

Neurodegeneration

Cellular Senescence

Mitochondria and Apoptosis³⁾

Mitochondria play a central role in the intrinsic (mitochondrial) pathway of apoptosis. Key mechanisms include:

·Cytochrome c Release: Upon apoptotic signals, mitochondrial outer membrane permeabilization (MOMP) occurs, leading to the release of cytochrome c into the cytoplasm.

·Caspase Cascade Activation: Cytochrome c binds to Apaf-1 (apoptotic protease activating factor-1), forming the apoptosome complex, which activates caspase-9. This activation triggers caspase-3, the executioner caspase, which dismantles cellular components, leading to cell death.

Mitochondria and Ferroptosis⁴⁾

Mitochondria contribute to ferroptosis, a type of regulated cell death characterized by iron dependency and lipid peroxidation:

·Iron Pathway: Mitochondria are central to iron-sulfur cluster biosynthesis and iron storage. Dysregulation of mitochondrial iron homeostasis can increase free iron, promoting the Fenton reaction and generation of reactive oxygen species (ROS).

·Lipid Peroxide Accumulation: Mitochondrial dysfunction can enhance the production of lipid peroxides, especially through the action of ROS on polyunsaturated fatty acids in membranes. Lipid peroxidation products accumulate and trigger ferroptosis.

Mitochondria and Cellular Senescence⁵⁾

Mitochondria are key regulators of cellular senescence, a state of irreversible cell cycle arrest often associated with aging and stress:

·mtDNA Damage: Mitochondrial DNA (mtDNA) is prone to damage due to its proximity to ROS production sites and limited repair mechanisms. Accumulation of mtDNA mutations can impair mitochondrial function, exacerbating senescence.

·ROS Production: Dysfunctional mitochondria generate excess ROS, which act as signaling molecules to reinforce senescence. ROS-mediated damage to cellular components further promotes the senescence-associated secretory phenotype (SASP), influencing neighboring cells.

Reference

1. Wallace, D. C. Mitochondria and cancer. Nature Reviews Cancer, 12(10), 685-698. 2 (2012).

2. Ziegler, D.V., Martin, N. & Bernard, D. Cellular senescence links mitochondria-ER contacts and aging. Commun Biol 4, 1323 (2021)

3. Xiong, S., Mu, T., Wang, G. et al. Mitochondria-mediated apoptosis in mammals. Protein Cell 5, 737–749 (2014)

4. Lyamzaev, K.G., Panteleeva, A.A., Simonyan, R.A. et al. The critical role of mitochondrial lipid peroxidation in ferroptosis: insights from recent studies. Biophys Rev 15, 875–885 (2023)

5. HIONA,A. The role of mitochondrial DNA mutations in aging and sarcopenia: Implications for the mitochondrial vicious cycle theory of aging.Exp. Gerontol. 43,24-33(2008)

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