Multi-factorial mitochondrial damage exhibits a "vicious circle" that leads to a progression of mitochondrial dysfunction and multi-organ adverse effects. Mitochondrial impairments (mitochondriopathies) are associated with severe pathologies including but not restricted to cancers, cardiovascular diseases, and neurodegeneration. However, the type and level of cascading pathologies are highly individual. Consequently, patient stratification, risk assessment, and mitigating measures are instrumental for cost-effective individualized protection. Therefore, the paradigm shift from reactive to predictive, preventive, and personalized medicine (3PM) is unavoidable in advanced healthcare. Flavonoids demonstrate evident antioxidant and scavenging activity are of great therapeutic utility against mitochondrial damage and cascading pathologies. In the context of 3PM, this review focuses on preclinical and clinical research data evaluating the efficacy of flavonoids as a potent protector against mitochondriopathies and associated pathologies.

• Klíčová slova
• anti-oxidant activity, cancer, cardiovascular disease, dysfunction, flavonoids, genoprotection, injury, mitochondrial function, mitochondrial impairment, mitochondriopathy, natural substances, neurodegeneration, patient stratification, phytochemicals, predictive preventive personalized medicine (PPPM/3PM), stress, tumorigenesis,
• MeSH
• antioxidancia farmakologie   terapeutické užití   MeSH
• cytoprotekce účinky léků   MeSH
• flavonoidy farmakologie   terapeutické užití   MeSH
• individualizovaná medicína metody   MeSH
• lidé MeSH
• mitochondriální nemoci diagnóza   prevence a kontrola   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• mitofagie účinky léků   MeSH
• oxidační stres účinky léků   MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antioxidancia MeSH
• flavonoidy MeSH

Cell growth and survival depend on a delicate balance between energy production and synthesis of metabolites. Here, we provide evidence that an alternative mitochondrial complex II (CII) assembly, designated as CIIlow, serves as a checkpoint for metabolite biosynthesis under bioenergetic stress, with cells suppressing their energy utilization by modulating DNA synthesis and cell cycle progression. Depletion of CIIlow leads to an imbalance in energy utilization and metabolite synthesis, as evidenced by recovery of the de novo pyrimidine pathway and unlocking cell cycle arrest from the S-phase. In vitro experiments are further corroborated by analysis of paraganglioma tissues from patients with sporadic, SDHA and SDHB mutations. These findings suggest that CIIlow is a core complex inside mitochondria that provides homeostatic control of cellular metabolism depending on the availability of energy.

• MeSH
• biosyntetické dráhy fyziologie   MeSH
• energetický metabolismus fyziologie   MeSH
• fyziologický stres * MeSH
• genový knockout MeSH
• HEK293 buňky MeSH
• kontrolní body fáze S buněčného cyklu fyziologie   MeSH
• lidé MeSH
• malá interferující RNA metabolismus   MeSH
• mitochondrie metabolismus   MeSH
• mutace MeSH
• myši inbrední BALB C MeSH
• myši nahé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• paragangliom genetika   patologie   MeSH
• respirační komplex II genetika   metabolismus   MeSH
• sukcinátdehydrogenasa genetika   metabolismus   MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• malá interferující RNA MeSH
• respirační komplex II MeSH
• respiratory complex II MeSH Prohlížeč
• SDHA protein, human MeSH Prohlížeč
• SDHB protein, human MeSH Prohlížeč
• sukcinátdehydrogenasa MeSH