Diet might affect male reproductive potential, but the biochemical mechanisms involved in the modulation of sperm quality remain poorly understood. While a Western diet is considered a risk factor ...for male infertility, the Mediterranean diet seems to protect against male infertility; moreover, the role of a vegetarian habitus in the preservation of sperm quality is controversial. The aim of this review is to analyze the molecular effects of single nutrients on sperm quality, focusing on their involvement in biochemical mechanisms related to sperm bioenergetics. It appears that diets rich in saturated fatty acids (SFA) and low in polyunsaturated fatty acids (PUFA) negatively affect sperm quality, whereas unsaturated fatty acids supplementation ameliorates sperm quality. In fact, the administration of PUFA, especially omega-3 PUFA, determined an increase in mitochondrial energetic metabolism and a reduction in oxidative damage. Carbohydrates and proteins are also nutritional modulators of oxidative stress and testosterone levels, which are strictly linked to sperm mitochondrial function, a key element for sperm quality. Moreover, many dietary natural polyphenols differentially affect (positively or negatively) the mitochondrial function, depending on their concentration. We believe that an understanding of the biochemical mechanisms responsible for sperm quality will lead to more targeted and effective therapeutics for male infertility.
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Non-alcoholic fatty liver disease(NAFLD) is a common clinicopathological condition, encompassing a range of conditions caused by lipid deposition within liver cells. To date, no approved drugs are ...available for the treatment of NAFLD, despite the fact that it represents a serious and growing clinical problem in the Western world. Identification of the molecular mechanisms leading to NAFLD-related fat accumulation, mitochondrial dysfunction and oxidative balance impairment facilitates the development of specific interventions aimed at preventing the progression of hepatic steatosis. In this review, we focus our attention on the role of dysfunctions in mitochondrial bioenergetics in the pathogenesis of fatty liver. Major data from the literature about the mitochondrial targeting of some antioxidant molecules as a potential treatment for hepatic steatosis are described and critically analysed. There is ample evidence of the positive effects of several classes of antioxidants, such as polyphenols(i.e., resveratrol, quercetin, coumestrol, anthocyanins, epigallocatechin gallate and curcumin), carotenoids(i.e., lycopene, astaxanthin and fucoxanthin) and glucosinolates(i.e., glucoraphanin, sulforaphane, sinigrin and allyl-isothiocyanate), on the reversion of fatty liver. Although the mechanism of action is not yet fully elucidated, in some cases an indirect interaction with mitochondrial metabolism is expected. We believe that such knowledge will eventually translate into the development of novel therapeutic approaches for fatty liver.
Non-alcoholic fatty liver disease(NAFLD)describes a range of conditions caused by fat deposition within liver cells.Liver fat content reflects the equilibrium between several metabolic pathways ...involved in triglyceride synthesis and disposal,such as lipolysis in adipose tissue and de novo lipogenesis,triglyceride esterification,fatty acid oxidation and very-low-density lipoprotein synthesis/secretion in hepatic tissue.In particular,it has been demonstrated that hepatic de novo lipogenesis plays a significant role in NAFLD pathogenesis.It is widely known that the fatty acid composition of the diet influences hepatic lipogenesis along with other metabolic pathways.Therefore,dietary fat may not only be involved in the pathogenesis of hepatic steatosis,but may also prevent and/or reverse hepatic fat accumulation.In this review,major data from the literature about the role of some dietary fats as a potential cause of hepatic fat accumulation or as a potential treatment for NAFLD are described.Moreover,biochemical mechanisms responsible for an increase or decrease in hepatic lipid content are critically analyzed.It is noteworthy that both quantitative and qualitative aspects of dietary fat influence triglyceride deposition in the liver.A high-fat diet or the dietary administration of conjugated linoleic acids induced hepatic steatosis.In contrast,supplementation of the diet with krill oil or pine nut oil helped in the prevention and/or in the treatment of steatotic liver.Quite interesting is the"case"of olive oil,since several studies have often provided different and or conflicting results in animal models.
After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite ...its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The yeast Saccharomyces cerevisiae is one of the most widely used model organisms for investigating various aspects of basic cellular functions that are conserved in human cells. This organism, as ...well as human cells, can modulate its metabolism in response to specific growth conditions, different environmental changes, and nutrient depletion. This adaptation results in a metabolic reprogramming of specific metabolic pathways. Mitochondrial carriers play a fundamental role in cellular metabolism, connecting mitochondrial with cytosolic reactions. By transporting substrates across the inner membrane of mitochondria, they contribute to many processes that are central to cellular function. The genome of Saccharomyces cerevisiae encodes 35 members of the mitochondrial carrier family, most of which have been functionally characterized. The aim of this review is to describe the role of the so far identified yeast mitochondrial carriers in cell metabolism, attempting to show the functional connections between substrates transport and specific metabolic pathways, such as oxidative phosphorylation, lipid metabolism, gluconeogenesis, and amino acids synthesis. Analysis of the literature reveals that these proteins transport substrates involved in the same metabolic pathway with a high degree of flexibility and coordination. The understanding of the role of mitochondrial carriers in yeast biology and metabolism could be useful for clarifying unexplored aspects related to the mitochondrial carrier network. Such knowledge will hopefully help in obtaining more insight into the molecular basis of human diseases.
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Differently from higher eukaryotic cells, in the yeast
there are two mitochondrial carrier proteins involved in the transport of citrate: Ctp1 and Yhm2. Very little is known about the physiological ...role of these proteins. Wild-type and mutant yeast strains deleted in
and
were grown in media supplemented with a fermentable (glucose) or a nonfermentable (ethanol) carbon source. To assess changes in Ctp1 and Yhm2 mRNA expression levels, real-time PCR was performed after total RNA extraction. In the wild-type strain, the metabolic switch from the exponential to the stationary phase is associated with an increase in the expression level of the two citrate transporters. In addition, the results obtained in the mutant strains suggest that the presence of a single citrate transporter can partially compensate for the absence of the other. Ctp1 and Yhm2 differently contribute to fermentative and respiratory metabolism. Moreover, the two mitochondrial carriers represent a link between the Krebs cycle and the glyoxylate cycle, which play a key role in the metabolic adaptation strategies of
.
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•Environmental factors play an important role in the decrease of male fertility.•Mitochondrial functionality is frequently used as an indicator of sperm quality.•Sperm mitochondria ...are target of potential endocrine disrupting chemicals.
The widespread cultivation of genetically modified organisms (GMOs) led to a widespread use of selective herbicides to which GMOs are resistant, thus increasing the concern about human exposure to them. Glyphosate (GLY) and glufosinate ammonium (GA), the active principles of the main formulations, have been investigated for their effects on human health, mainly cancer and reproductive toxicity. However, little is known about their effects on the molecular mechanisms related to sperm quality.
To investigate the effects of GLY and GA on mitochondrial respiration efficiency, we took advantage of our already established ex vivo human sperm mitochondria assay. Since spermatozoa are highly regulated by sex steroids, we tested at first testosterone (T), di-hydroxytestosterone (DHT), 17β-estradiol (E2) and progesterone (P4). Then, we tested the effects of GLY and GA and of the hormone-like flavonoid quercetin (QRC) in a dose-dependent manner. The 0.1−1000 nM concentration range has been considered because it covers both the sexual hormones physiologically relevant concentrations (10 nM), triggering endogenously hormone-dependent signaling pathways, and the estimated (nM range) QRC dietary intake. Subsequently, co-incubation experiments were carried out with the two herbicides in the presence of 10 nM of each sex steroid and QRC.
We found that: i) DHT and QRC are able to significantly reduce mitochondrial functionality at concentrations ≥ 10 nM; ii) GLY and GA negatively affect mitochondrial respiration efficiency; iii) in the presence of 10 nM DHT, the negative effect of GLY was increased; iiii) DHT, QRC and GA target mitochondria by using a mechanism different from GLY.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The cytochrome bc1 complex is an essential component of the mitochondrial respiratory chain of the yeast Saccharomyces cerevisiae. It is composed of ten protein subunits, three of them playing an ...important role in electron transfer and proton pumping across the inner mitochondrial membrane. Cytochrome b, the central component of this respiratory complex, is encoded by the mitochondrial genome, whereas all the other subunits are of nuclear origin. The assembly of all these subunits into the mature and functional cytochrome bc1 complex is therefore a complicated process which requires the participation of several chaperone proteins. It has been found that the assembly process of the mitochondrial bc1 complex proceeds through the formation of distinct sub-complexes in an ordered sequence. Most of these sub-complexes have been thoroughly characterized, and their molecular compositions have also been defined. This study critically analyses the results obtained so far and highlights new possible areas of investigation.
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Sperm motility is the most important parameter involved in the fertilization process and it is strictly required for reproductive success. Although sperm movements are essential for the physiologic ...fertilization process, the data, deriving from studies focused on the research of altered cell pathways involved in asthenozoospermia, offer only limited information about the molecular mechanism underlying sperm motility. The aim of this study was to identify proteins involved in human sperm motility deficiency by using label-free mass-spectrometry liquid chromatography (LC-MS/MS). For this purpose, we selected sperm samples with three different classes of progressive motility: low, medium (asthenozoospermic samples) and high (normozoospermic samples). We found that several differential expressed proteins in asthenozoospermic samples were related to energetic metabolism, suggesting an interesting link between bioenergetics pathways and the regulation of sperm motility, necessary for the flagellum movement. Therefore, our results provide strong evidence that mass spectrometry-based proteomics represents an integrated approach to detect novel biochemical markers of sperm motility and quality with diagnostic relevance for male infertility and unravel the molecular etiology of idiopathic cases.
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Sperm cells progressive motility is the most important parameter involved in the fertilization process. Sperm middle piece contains mitochondria, which play a critical role in energy production and ...whose proper operation ensures the reproductive success. Notably, sperm progressive motility is strictly related to mitochondrial membrane potential (MMP) and consequently to mitochondrial functionality. Although previous studies presented an evaluation of mitochondrial function through MMP assessment in entire sperm cells samples, a quantitative approach at single-cell level could provide more insights in the analysis of semen quality. Here we combine laser scanning confocal microscopy and functional fluorescent staining of mitochondrial membrane to assess MMP distribution among isolated spermatozoa. We found that the sperm fluorescence value increases as a function of growing progressive motility and that such fluorescence is influenced by MMP disruptors, potentially allowing for the discrimination of different quality classes of sperm cells in heterogeneous populations.
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