Mitochondria are essential organelles in physiology and kidney diseases, because they produce cellular energy required to perform their function. During mitochondrial metabolism, reactive oxygen species (ROS) are produced. ROS function as secondary messengers, inducing redox-sensitive post-translational modifications (PTM) in proteins and activating or deactivating different cell signaling pathways. However, in kidney diseases, ROS overproduction causes oxidative stress (OS), inducing mitochondrial dysfunction and altering its metabolism and dynamics. The latter processes are closely related to changes in the cell redox-sensitive signaling pathways, causing inflammation and apoptosis cell death. Although mitochondrial metabolism, ROS production, and OS have been studied in kidney diseases, the role of redox signaling pathways in mitochondria has not been addressed. This review focuses on altering the metabolism and dynamics of mitochondria through the dysregulation of redox-sensitive signaling pathways in kidney diseases.

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Head and neck squamous cell carcinoma (HNSCC) cells that are positive for human papillomavirus (HPV+) favor mitochondrial metabolism rather than glucose metabolism. However, the involvement of mitochondrial metabolism in HNSCC HPV+ cells is still unknown. The aim of this work was to evaluate the role of E6 oncoproteins from HPV16 and HPV18 in the mitochondrial metabolism in an HNSCC model. We found that E6 from both viral types abates the phosphorylation of protein kinase B-serine 473 (pAkt), which is associated with a shift in mitochondrial metabolism. E6 oncoproteins increased the levels of protein subunits of mitochondrial complexes (I to IV), as well as the ATP synthase and the protein levels of the voltage dependent anion channel (VDAC). Although E6 proteins increased the basal and leak respiration, the ATP-linked respiration was not affected, which resulted in mitochondrial decoupling. This increase in leak respiration was associated to the induction of oxidative stress (OS) in cells expressing E6, as it was observed by the fall in the glutathione/glutathione disulfide (GSH/GSSG) rate and the increase in reactive oxygen species (ROS), carbonylated proteins, and DNA damage. Taken together, our results suggest that E6 oncoproteins from HPV16 and HPV18 are inducers of mitochondrial metabolism.

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Oxidative stress (OS) has greatly interested the research community in understanding damaging processes occurring in cells. OS is triggered by an imbalance between reactive oxygen species (ROS) production and their elimination by the antioxidant system; however, ROS function as second messengers under physiological conditions. ROS are produced from endogenous and exogenous sources. Endogenous sources involve mitochondria, nicotinamide adenine dinucleotide phosphate hydrogen (NADPH), oxidases (NOXs), endoplasmic reticulum (ER), xanthine oxidases (XO), endothelial nitric oxide synthase (eNOs), and others. In contrast, exogenous ROS might be generated through ultraviolet (UV) light, ionizing radiation (IR), contaminants, and heavy metals, among others. It can damage DNA, lipids, and proteins if OS is not controlled. To avoid oxidative damage, antioxidant systems are activated. In the present review, we focus on the basic concepts of OS, highlighting the production of reactive oxygen and nitrogen species (RONS) derived from internal and external sources and the last elimination. Moreover, we include the cellular antioxidant system regulation and their ability to decrease OS. External antioxidants are also proposed as alternatives to ameliorate OS. Finally, we review diseases involving OS and their mechanisms.

Severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2) causes coronavirus disease 2019 (COVID‐19), characterised by high levels of inflammation and oxidative stress (OS). Oxidative stress induces oxidative damage to lipids, proteins, and DNA, causing tissue damage. Both inflammation and OS contribute to multi‐organ failure in severe cases. Magnesium (Mg 2+ ) regulates many processes, including antioxidant and anti‐inflammatory responses, as well as the proper functioning of other micronutrients such as vitamin D. In addition, Mg 2+ participates as a second signalling messenger in the activation of T cells. Therefore, Mg 2+ deficiency can cause immunodeficiency, exaggerated acute inflammatory response, decreased antioxidant response, and OS. Supplementation with Mg 2+ has an anti‐inflammatory response by reducing the levels of nuclear factor kappa B (NF‐κB), interleukin (IL) ‐6, and tumor necrosis factor alpha. Furthermore, Mg 2+ supplementation improves mitochondrial function and increases the antioxidant glutathione (GSH) content, reducing OS. Therefore, Mg 2+ supplementation is a potential way to reduce inflammation and OS, strengthening the immune system to manage COVID‐19. This narrative review will address Mg 2+ deficiency associated with a worse disease prognosis, Mg 2+ supplementation as a potent antioxidant and anti‐inflammatory therapy during and after COVID‐19 disease, and suggest that randomised controlled trials are indicated.

Summary While high‐risk human papillomavirus (HR‐HPV) infection is related to the development of cervical, vulvar, anal, penile and oropharyngeal cancer, low‐risk human papillomavirus (LR‐HPV) infection is implicated in about 90% of genital warts, which rarely progress to cancer. The carcinogenic role of HR‐HPV is due to the overexpression of HPV E5, E6 and E7 oncoproteins which target and modify cellular proteins implicated in cell proliferation, apoptosis and immortalization. LR‐HPV proteins also target and modify some of these processes; however, their oncogenic potential is lower than that of HR‐HPV. HR‐HPVs have substantial differences with LR‐HPVs such as viral integration into the cell genome, induction of p53 and retinoblastoma protein degradation, alternative splicing in HR‐HPV E6‐E7 open reading frames, among others. In addition, LR‐HPV can activate the autophagy process in infected cells while HR‐HPV infection deactivates it. However, in cancer HR‐HPV might reactivate autophagy in advance stages. Autophagy is a catabolic process that maintains cell homoeostasis by lysosomal degradation and recycling of damaged macromolecules and organelles; nevertheless, depending upon cellular context autophagy may also induce cell death. Therefore, autophagy can contribute either as a promotor or as a suppressor of tumours. In this review, we focus on the role of HR‐HPV and LR‐HPV in autophagy during viral infection and cancer development. Additionally, we review key regulatory molecules such as microRNAs in HPV present during autophagy, and we emphasize the potential use of cancer treatments associated with autophagy in HPV‐related cancers.