Space travel has advanced significantly over the last six decades with astronauts spending up to 6 months at the International Space Station. Nonetheless, the living environment while in outer space is extremely challenging to astronauts. In particular, exposure to space radiation represents a serious potential long‐term threat to the health of astronauts because the amount of radiation exposure accumulates during their time in space. Therefore, health risks associated with exposure to space radiation are an important topic in space travel, and characterizing space radiation in detail is essential for improving the safety of space missions. In the first part of this review, we provide an overview of the space radiation environment and briefly present current and future endeavors that monitor different space radiation environments. We then present research evaluating adverse biological effects caused by exposure to various space radiation environments and how these can be reduced. We especially consider the deleterious effects on cellular DNA and how cells activate DNA repair mechanisms. The latest technologies being developed, e.g., a fluorescent ubiquitination‐based cell cycle indicator, to measure real‐time cell cycle progression and DNA damage caused by exposure to ultraviolet radiation are presented. Progress in examining the combined effects of microgravity and radiation to animals and plants are summarized, and our current understanding of the relationship between psychological stress and radiation is presented. Finally, we provide details about protective agents and the study of organisms that are highly resistant to radiation and how their biological mechanisms may aid developing novel technologies that alleviate biological damage caused by radiation. Future research that furthers our understanding of the effects of space radiation on human health will facilitate risk‐mitigating strategies to enable long‐term space and planetary exploration.

Mitochondrial reverse electron transport (RET) represents a fundamental but potentially hazardous metabolic process in eukaryotic cells. This review systematically examines current understanding of RET mechanisms and their pathophysiological consequences. RET occurs when electrons flow inversely from reduced coenzyme Q (CoQH₂) to complex I, driven by excessive reduction of the CoQ pool and elevated mitochondrial membrane potential, resulting in substantial superoxide production. While moderate RET contributes to physiological redox signaling, sustained RET activation leads to oxidative damage and activates regulated cell death pathways. Notably, RET demonstrates metabolic duality: it facilitates ATP generation through NAD⁺ reduction while simultaneously inducing mitochondrial dysfunction via reactive oxygen species overproduction. Pathologically, RET has been implicated in myocardial ischemia–reperfusion injury, neurodegenerative disorders including Alzheimer’s diseases, and exhibits context-dependent roles in tumor progression. Emerging evidence also suggests RET involvement in microbial pathogenesis through modulation of host immune responses. These findings position RET as a critical regulatory node in cellular metabolism with broad implications for human diseases. Future investigations should focus on developing tissue-specific RET modulators and elucidating the molecular switches governing its activation threshold, which may yield novel therapeutic strategies for diverse pathological conditions.

Mitochondrial dysfunction is a key early pathological process in neurodegenerative diseases (NDs), leading to oxidative stress, impaired energy metabolism, and neuronal apoptosis prior to the onset of clinical symptoms. Although mitochondria represent important therapeutic targets, effective interventions targeting mitochondrial function remain limited. This review summarizes current evidence regarding the mechanisms by which melatonin protects mitochondria and evaluates its therapeutic relevance, with a primary focus on Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease—the major protagonists of NDs—while briefly covering other NDs such as amyotrophic lateral sclerosis, multiple sclerosis, and prion diseases. Melatonin selectively accumulates in neuronal mitochondria and exerts neuroprotection through multiple pathways: (1) direct scavenging of reactive oxygen species (ROS); (2) transcriptional activation of antioxidant defenses via the SIRT3 and Nrf2 pathways; (3) regulation of mitochondrial dynamics through DRP1 and OPA1; and (4) promotion of PINK1- and Parkin-mediated mitophagy. Additionally, melatonin exhibits context-dependent pleiotropy: under conditions of mild mitochondrial stress, it restores mitochondrial homeostasis; under conditions of severe mitochondrial damage, it promotes pro-survival autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby conferring stage-specific therapeutic advantages. Overall, melatonin offers a sophisticated mitochondria-targeting strategy for the treatment of NDs. However, successful clinical translation requires clarification of receptor-dependent signaling pathways, development of standardized dosing strategies, and validation in large-scale randomized controlled trials.

Radiotherapy remains a cornerstone in cancer treatment, leveraging ionizing radiation to eradicate malignant cells. Its efficacy, however, is frequently challenged by the heterogeneous sensitivity of tumors and surrounding tissues to radiation. Therefore, understanding the molecular mechanisms underlying radiosensitivity is crucial for improving treatment outcomes. Among the myriad of molecular players involved, the tumor suppressor protein p53 stands out as a central regulator with significant implications for radiosensitivity. Known as the “guardian of the genome”, p53 plays a pivotal role in maintaining genomic stability and orchestrating cellular responses such as cell cycle arrest, DNA repair, apoptosis, and senescence in response to various stress signals, including radiation-induced DNA damage. Activation of p53 triggers the transcription of target genes involved in DNA repair pathways, such as p21, MDM2, and GADD45, facilitating the repair of radiation-induced DNA damage or the elimination of irreparably damaged cells. This, in turn, influences the overall radiosensitivity of tissues. Mutations in the TP53 gene, which encodes p53, are among the most frequent genetic alterations in human cancers. Loss or dysfunction of p53 can compromise the cellular response to radiation, leading to increased resistance to therapy and poorer clinical outcomes. Conversely, intact p53 function is associated with enhanced radiosensitivity due to its ability to promote cell cycle arrest and apoptosis in response to radiation-induced DNA damage. In conclusion, elucidating the molecular mechanisms by which p53 influences radiosensitivity is essential for advancing our understanding of the radiation response in cancer cells and developing more effective therapeutic approaches to cancer treatment. This review provides a comprehensive overview of the multifaceted role of p53 in modulating cellular responses to radiation, emphasizing its influence on radiosensitivity.

Radiotherapy remains currently a critical component for both primary and metastatic brain tumors either alone or in combination with surgery, chemotherapy, and molecularly targeted agents, while it could cause simultaneously normal brain tissue injury leading to serious health consequences, that is, development of cognitive impairments following cranial radiotherapy is considered as a critical clinical disadvantage especially for the whole brain radiotherapy. Biomarkers can help to detect the accurate physiology or conditions of patients with brain tumor and develop effective treatment procedures for these patients. In the near future, biomarkers will become one of the prime driving forces of cancer treatment. In this minireview, we analyze the documented work on the acute brain damage and late consequences induced by radiotherapy, identify the biomarkers, in particular, the predictive biomarkers for the damage, and summarize the biological significance of the biomarkers. It is expected that translation of these research advance to radiotherapy would assist stratifying patients for optimized treatment and improving therapeutic efficacy and the quality of life.

Radiation exposure poses significant health risks, particularly in radiotherapy and nuclear accidents. Certain dietary ingredients offer potential radioprotection and radiosensitization. In this review, we explore the impact of dietary ingredients, including vitamins, minerals, antioxidants, and other bioactive compounds, on radiation sensitivity and their potential for radioprotection. Radiosensitizers reoxygenate hypoxic tumor cells, increase the radiolysis of water molecules, and regulate various molecular mechanisms to induce cytotoxicity and inhibit DNA repair in irradiated tumor cells. Several dietary ingredients, such as vitamins C, E, selenium, and phytochemicals, show promise in protecting against radiation by reducing radiation-induced oxidative stress, inflammation, and DNA damage. Radioprotectors, such as ascorbic acid, curcumin, resveratrol, and genistein, activate and modulate various signaling pathways, including Keap1-Nrf2, NF-κB, PI3K/Akt/mammalian target of rapamycin (mTOR), STAT3, and mitogen-activated protein kinase (MAPK), in response to radiation-induced oxidative stress, regulating inflammatory cytokine expression, and promoting DNA damage repair and cell survival. Conversely, natural dietary radiosensitizers impede these pathways by enhancing DNA damage and inducing apoptosis in irradiated tumor cells. Understanding the molecular basis of these effects may aid in the development of effective strategies for radioprotection and radiosensitization in cancer treatment. Dietary interventions have the potential to enhance the efficacy of radiation therapy and minimize the side effects associated with radiation exposure.