Cellular Function Analysis for

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)

Back to Top