BACKGROUND: Besides adenine triphosphate (ATP) production for sustaining motility, the mitochondria of sperm also host other critical cellular functions during germ cell development and fertilization including calcium homeostasis, generation of reactive oxygen species (ROS), apoptosis, and in some cases steroid hormone biosynthesis. Normal mitochondrial membrane potential with optimal mitochondrial performance is essential for sperm motility, capacitation, acrosome reaction, and DNA integrity.
RESULTS: Defects in the sperm mitochondrial function can severely harm the fertility potential of males. The role of sperm mitochondria in fertilization and its final fate after fertilization is still controversial. Here, we review the current knowledge on human sperm mitochondria characteristics and their physiological and pathological conditions, paying special attention to improvements in assistant reproductive technology and available treatments to ameliorate male infertility.
CONCLUSIONS: Although mitochondrial variants associated with male infertility have potential clinical use, research is limited. Further understanding is needed to determine how these characteristics lead to adverse pregnancy outcomes and affect male fertility potential.

The mitochondria are responsible for the production of cellular ATP, the regulation of cytosolic calcium levels, and the organization of numerous apoptotic proteins through the release of cofactors necessary for the activation of caspases. This level of functional adaptability can only be attained by sophisticated structural alignment. The morphology of the mitochondria does not remain unchanged throughout time; rather, it undergoes change as a result of processes known as fusion and fission. Fzo in flies, Fzo1 in yeast, and mitofusins in mammals are responsible for managing the outer mitochondrial membrane fusion process, whereas Mgm1 in yeast and optic atrophy 1 in mammals are responsible for managing the inner mitochondrial membrane fusion process. The fusion process is composed of two phases. MFN1, a GTPase that is located on the outer membrane of the mitochondria, is involved in the process of linking nearby mitochondria, maintaining the potential of the mitochondrial membrane, and apoptosis. This article offers specific information regarding the functions of MFN1 in a variety of cells and organs found in living creatures. According to the findings of the literature review, MFN1 plays an important part in a number of diseases and organ systems; nevertheless, the protein\'s function in other disease models and cell types has to be investigated in the near future so that it can be chosen as a promising marker for the therapeutic and diagnostic potentials it possesses. Overall, the major findings of this review highlight the pivotal role of mitofusin (MFN1) in regulating mitochondrial dynamics and its implications across various diseases, including neurodegenerative disorders, cardiovascular diseases, and metabolic syndromes. Our review identifies novel therapeutic targets within the MFN1 signaling pathways and underscores the potential of MFN1 modulation as a promising strategy for treating mitochondrial-related diseases. Additionally, the review calls for further research into MFN1\'s molecular mechanisms to unlock new avenues for clinical interventions, emphasizing the need for targeted therapies that address MFN1 dysfunction.

3,4-Methylenedioxymethamphetamine (MDMA or \"ecstasy\") is a drug of abuse used by millions worldwide. MDMA human abuse and dependence is well described, but addictive properties are not always consistent among studies. This amphetamine is a substrate type releaser, binding to monoamine transporters, leading to a pronounced release of serotonin and noradrenaline and to a minor extent dopamine. The toxicity of MDMA is well studied at the pre-clinical level, with neurotoxicity and hepatotoxicity being particularly described. In this review, we describe the most relevant MDMA effects at the mitochondrial level found in in vitro and in vivo models, these later conducted in mice and rats. Most of these reports focus on the mitochondria of brain or liver. In in vitro models, MDMA causes depletion of ATP levels and inhibition of mitochondrial complex I and III, loss in mitochondrial membrane potential (ΔΨm) and induction of mitochondrial permeability transition. The involvement of mitochondria in the apoptotic cell death evoked by MDMA has also been shown, such as the release of cytochrome c. Additionally, MDMA or its metabolites impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria. In animal studies, MDMA decreased mitochondrial complex I activity and decreased ATP levels. Moreover, MDMA-evoked oxidative stress has been shown to cause deletion on mitochondrial DNA and impairment in mitochondrial protein synthesis. Although the concentrations and doses used in some studies do not always correlate to the human scenario, the mitochondrial abnormalities evoked by MDMA are well described and are in part responsible for its mechanism of toxicity.

Invasive infections caused by Candida that are resistant to clinically available antifungals are of increasing concern. Increasing rates of fluconazole resistance in non-albicans Candida species have been documented in multiple countries on several continents. This situation has been further exacerbated over the last several years by Candida auris, as isolates of this emerging pathogen that are often resistant to multiple antifungals. T-2307 is an aromatic diamidine currently in development for the treatment of invasive fungal infections. This agent has been shown to selectively cause the collapse of the mitochondrial membrane potential in yeasts when compared to mammalian cells. In vitro activity has been demonstrated against Candida species, including C. albicans, C. glabrata, and C. auris strains, which are resistant to azole and echinocandin antifungals. Activity has also been reported against Cryptococcus species, and this has translated into in vivo efficacy in experimental models of invasive candidiasis and cryptococcosis. However, little is known regarding the clinical efficacy and safety of this agent, as published data from studies involving humans are not currently available.

Following the discovery that caloric restriction extends the lifespan of many species of animals, the free radical theory of aging attributes the occurrence of oxidized nucleic acids, proteins, and lipids to reactive oxygen radical species originating from the metabolism of foods and the diminished efficacy of oxidative metabolism. Because of the decline of many critical neuro-hormones in aging, the neuroendocrine theory of aging attributes these changes to reduced feedback control of hormone production by the hypothalamus. Several rare genetic diseases attribute accelerated aging to changes in deoxyribonucleic acid (DNA) repair, depletion of the coenzyme nicotinamide adenine dinucleotide (NAD+), and altered methionine and homocysteine metabolism. The theory of oxidative phosphorylation attributes mitochondrial adenosine triphosphate (ATP) synthesis to the active site, thioretinaco ozonide oxygen NAD+ phosphate, which couples polymerization of NAD+ and phosphate to ATP produced by reduction of oxygen by electrons derived from foods. Loss of the thioretinaco ozonide oxygen ATP complex from the opening of the mitochondrial permeability transition pore (mPTP) is proposed to explain the abnormalities of oxidative metabolism occurring in cellular aging and carcinogenesis, thereby uniting the free radical and neuroendocrine theories of aging. Cellular senescence is associated with shortening of telomeres and decreased activity of telomerase, and exposure of cultured endothelial cells to homocysteine causes cellular senescence, shortened telomeres, and increased acidic β-galactosidase, a marker of cellular senescence. The decrease in telomerase with aging is related to decreased nitric oxide production by nitric oxide synthase. The pathogenic microbes occurring in atherosclerotic plaques and in cerebral plaques in dementia inhibit nitric oxide synthesis by up-regulation of polyamine biosynthesis from adenosyl methionine and putrescene, causing the hyperhomocysteinemia and suppressed immunity that is observed in atherosclerosis and dementia. Progressive mitochondrial dysfunction occurs in aging because of loss of the thioretinaco ozonide oxygen ATP complex from mitochondrial membranes by opening of the mitochondrial permeability transition pore. Melatonin, a neuro-hormone, and cycloastragenol, a telomerase activator, both prevent mitochondrial dysfunction by inhibition of mPTP pore opening. The carcinogenic effects of radiofrequency radiation and mycotoxins are attributed to loss of thioretinaco ozonide from opening of the mPTP and decomposition of the active site of oxidative phosphorylation. The anti-aging effects of retinoids, the decreased concentration of cerebral cobalamin coenzymes in aging, and the diminished concentration of NAD+ from sirtuin activation, as observed in aging, all support the concept of loss of the thioretinaco ozonide oxygen ATP active site from mitochondria as the cause of decreased oxidative phosphorylation and mitochondrial dysfunction in aging.

By generating the majority of a cell\'s ATP, mitochondria permit a vast range of reactions necessary for life. Mitochondria also perform other vital functions including biogenesis and assembly of iron-sulfur proteins, maintenance of calcium homeostasis, and activation of apoptosis. Accordingly, mitochondrial dysfunction has been linked with the pathology of many clinical conditions including cancer, type 2 diabetes, cardiomyopathy, and atherosclerosis. The ongoing maintenance of mitochondrial structure and function requires the import of nuclear-encoded proteins and for this reason, mitochondrial protein import is indispensible for cell viability. As mitochondria play central roles in determining if cells live or die, a comprehensive understanding of mitochondrial structure, protein import, and function is necessary for identifying novel drugs that may destroy harmful cells while rescuing or protecting normal ones to preserve tissue integrity. This review summarizes our current knowledge on mitochondrial architecture, mitochondrial protein import, and mitochondrial function. Our current comprehension of how mitochondrial functions maintain cell homeostasis and how cell death occurs as a result of mitochondrial stress are also discussed.

This review summarizes the literature on mammalian toxicity of ZnO nanoparticles (NPs) published between 2009 and 2011. The toxic effects of ZnO NPs are due to the compound\'s solubility. Whether the increased intracellular [Zn(2+)] is due to the NPs being taken up by cells or to NP dissolution in medium is still unclear. In vivo airway exposure poses an important hazard. Inhalation or instillation of the NPs results in lung inflammation and systemic toxicity. Reactive oxygen species (ROS) generation likely plays an important role in the inflammatory response. The NPs do not, or only to a minimal extent, cross the skin; this also holds for sunburned skin. Intraperitoneal administration induces neurological effects. The NPs show systemic distribution; target organs are liver, spleen, lung, and kidney and, in some cases, the heart. In vitro exposure of BEAS-2B bronchial epithelial cells and A549 alveolar adenocarcinoma cells results in cytotoxicity, increased oxidative stress, increased intracellular [Ca(2+)], decreased mitochondrial membrane potential, and interleukin (IL)-8 production. Decreased contractility of airway smooth muscle cells poses an additional hazard. In contrast to the results for BEAS-2B and A549 cells, in RKO colon carcinoma cells ZnO NPs and not Zn(2+) induce cytotoxicity and mitochondrial dysfunction. Short-term exposure of skin cells results in apoptosis but not in an inflammatory response, while long-term exposure leads to increased ROS generation, decreased mitochondrial activity, and formation of tubular intercellular structures. Macrophages, monocytes, and dendritic cells are affected; exposure results in cytotoxicity, oxidative stress, intracellular Ca(2+) flux, decreased mitochondrial membrane potential, and production of IL-1β and chemokine CXCL9. The NPs are phagocytosed by macrophages and dissolved in lysosomes. In vitro the Comet assay and the cytokinesis-blocked micronucleus assay show genotoxicity, whereas the Ames test does not. This is, however, not confirmed by in vivo genotoxicity assays. Protein binding results in increased stability.