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Mitochondria are bilayer membrane organelles with basic metabolic activity. They are considered hubs for biosynthesis, bioenergy, and signaling functions, coordinating major biological pathways. Mitochondria are coupled to the oxidation of fatty acids and pyruvate through electron transport chains and have historically been considered the primary source of cellular energy. Recent studies have depicted that mitochondria are centers that promote inflammatory responses and play a crucial role in combating pathogenic infections. Moreover, Show less

Colorectal cancer (CRC) exhibits significant diversity and heterogeneity, posing a requirement for novel therapeutic targets. Polysulfides are associated with CRC progression and immune evasion, but the underlying mechanisms are not fully understood. Sulfide: quinone oxidoreductase (SQR), a mitochondrial flavoprotein, catalyzes hydrogen sulfide (H₂S) oxidation and polysulfides production. Herein, we explored its role in CRC pathogenesis and its potential as a therapeutic target. Our findings revealed that SQR knockout disrupted polysulfides homeostasis, diminished mitochondrial function, impaired cell proliferation, and triggered early apoptosis in HCT116 CRC cells. Moreover, the SQR knockout led to markedly reduced tumor sizes in mice models of colon xenografts. Although the transcription of glycolytic genes remained largely unchanged, metabolomic analysis demonstrated a reprogramming of glycolysis at the fructose-1,6-bisphosphate degradation step, catalyzed by aldolase A (ALDOA). Both Western blot analysis and enzymatic assays confirmed the decrease in ALDOA levels and activity. In conclusion, the study establishes the critical role of SQR in mitochondrial function and metabolic regulation in CRC, with its knockout leading to metabolic reprogramming and diminished tumor growth in HCT116 tumor xenografts. These insights lay a foundation for the development of SQR-targeted therapies for CRC. Show less

Non‑small cell lung cancer (NSCLC) is one of the most prevalent and lethal types of cancers worldwide and its high incidence and mortality rates pose a significant public health challenge. Despite significant advances in targeted therapy and immunotherapy, the overall prognosis of patients with NSCLC remains poor. Hypoxia is a critical driving factor in tumor progression, influencing the biological behavior of tumor cells through complex molecular mechanisms. The present review systematically examined the role of the hypoxic microenvironment in NSCLC, demonstrating its crucial role in promoting tumor cell growth, invasion and metastasis. Additionally, it has been previously reported that the hypoxic microenvironment enhances tumor cell resistance by activating hypoxia‑inducible factor and regulating exosome secretion. The hypoxic microenvironment also enables tumor cells to adapt to low oxygen and nutrient‑deficient conditions by enhancing metabolic reprogramming, such as through upregulating glycolysis. Further studies have shown that the hypoxic microenvironment facilitates immune escape by modulating tumor‑associated immune cells and suppressing the antitumor response of the immune system. Moreover, the hypoxic microenvironment increases tumor resistance to radiotherapy, chemotherapy and other types of targeted therapy through various pathways, significantly reducing the therapeutic efficacy of these treatments. Therefore, it could be suggested that early detection of cellular hypoxia and targeted therapy based on hypoxia may offer new therapeutic approaches for patients with NSCLC. The present review not only deepened the current understanding of the mechanisms of action and role of the hypoxic microenvironment in NSCLC but also provided a solid theoretical basis for the future development of precision treatments for patients with NSCLC. Show less