Adenine nucleotide translocator 4 (Ant4), an ATP/ADP transporter expressed in the early phases of spermatogenesis, plays a crucial role in male fertility. While Ant4 loss causes early arrest of meiosis and increased apoptosis of spermatogenic cells in male mice, its other potential functions in male fertility remain unexplored. Here, we utilized Ant4 knockout mice to delineate the effects of Ant4-deficiency on male reproduction. Our observations demonstrated that Ant4-deficiency led to infertility and impaired testicular development, which was further investigated by evaluating testicular oxidative stress, autophagy, and inflammation. Specifically, the loss of Ant4 led to an imbalance of oxidation and antioxidants. Significant ultrastructural alterations were identified in the testicular tissues of Ant4-deficient mice, including swelling of mitochondria, loss of cristae, and accumulation of autophagosomes. Our results also showed that autophagic flux and AKT-AMPK-mTOR signaling pathway were affected in Ant4-deficient mice. Moreover, Ant4 loss increased the expression of pro-inflammatory factors. Overall, our findings underscored the importance of Ant4 in regulating oxidative stress, autophagy, and inflammation in testicular tissues. Taken together, these insights provided a nuanced understanding of the significance of Ant4 in testicular development.

Possible pathways by which brassinosteroids affect the monooxygenase enzymatic system of mammalian liver microsomes, which is involved in the transformation of a broad spectrum of xenobiotics, were...

Introduction: Toxic hepatitis is characterized by enhanced oxidative stress and disruption of antioxidant defensemechanisms in the liver mitochondria. In this study, we investigated the effects of polyphenolic extracts (Helmar-1 and Helmar-2) obtained from Helichrysum maracandicum on mitochondrial antioxidant systems in ratswith experimentally induced toxic hepatitis.Methods: Experimental toxic hepatitis was established in rats through intraperitoneal administration of carbontetrachloride (CCl₄) diluted in olive oil (50%, 1 mL/kg), administered twice weekly over a two-week period. Liverinjury was verified by elevated plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase(AST). The animals were subsequently treated with Helmar-1 and Helmar-2 extracts at a dose of 20 mg/kg per dayfor 10 consecutive days. The activities of key antioxidant enzymes (superoxide dismutase, catalase, and glutathioneperoxidase), malondialdehyde (MDA) content, and mitochondrial respiration and oxidative phosphorylationparameters (V₂, V₃, V₄, RCR, and ADP/O ratio) were assessed in liver mitochondria.Results: Treatment with both Helmar-1 and Helmar-2 extracts resulted in a significant enhancement of antioxidantenzyme activities, a marked reduction in MDA levels, and substantial improvement in mitochondrial respirationand oxidative phosphorylation parameters compared to untreated toxic hepatitis groups.Conclusion: Overall, these results confirm that Helichrysum maracandicum polyphenol extracts improve mitochondrial respiration, oxidative phosphorylation efficiency, antioxidant defense, and membrane stability in toxic hepatitis.

The state of lipid peroxidation (LPO), respiration and oxidative phosphorylation, mitochondrial permeability transition pore (mPTP), and the antiradical activity of rat liver mitochondria in the streptozotocin (STZ)-induced diabetes condition were studied with the consideration of the ways of correcting detected membrane damages using gossitan isolated from the cotton plant Gossypium hirsutum L. It was shown that the rate of respiration of liver mitochondria in states V3 and V4 increases during STZ-induced diabetes, which significantly reduces the respiratory control (RC) and ADP/O coefficients in comparison with the control. The findings suggest that the uncoupling of respiration and oxidative phosphorylation takes place during STZ-induced diabetes. It was shown that in the STZ-induced diabetes condition, the rate of swelling of rat liver mitochondria is higher than that of the healthy ones; this means that mPTP of rat liver mitochondria is in the open state. Gossitan recovers mPTP to the normal condition, thereby removing the STZ effect on mitochondria. Gossitan (a personal dose is 10 mg/kg of body weight, during 8 days) eliminates the detected functional disorders of rat liver mitochondria, probably due to its antioxidant properties.