Therapies intended to mitigate cardiovascular complications cannot be applied in practice without detailed knowledge of molecular mechanisms. Mitochondria, as the end-effector of cardioprotection, represent one of the possible therapeutic approaches. The present review provides an overview of factors affecting the regulation processes of mitochondria at the level of mitochondrial permeability transition pores (mPTP) resulting in comprehensive myocardial protection. The regulation of mPTP seems to be an important part of the mechanisms for maintaining the energy equilibrium of the heart under pathological conditions. Mitochondrial connexin 43 is involved in the regulation process by inhibition of mPTP opening. These individual cardioprotective mechanisms can be interconnected in the process of mitochondrial oxidative phosphorylation resulting in the maintenance of adenosine triphosphate (ATP) production. In this context, the degree of mitochondrial membrane fluidity appears to be a key factor in the preservation of ATP synthase rotation required for ATP formation. Moreover, changes in the composition of the cardiolipin’s structure in the mitochondrial membrane can significantly affect the energy system under unfavorable conditions. This review aims to elucidate functional and structural changes of cardiac mitochondria subjected to preconditioning, with an emphasis on signaling pathways leading to mitochondrial energy maintenance during partial oxygen deprivation.

The effect of the deletion of a 57 bp native signal sequence, which transports the nascent protein through the endoplasmic reticulum membrane in plants, on improved AtTGG1 plant myrosinase production in Pichia pastoris was studied. Myrosinase was extracellularly produced in a 3-liter laboratory fermenter using α-mating factor as the secretion signal. After the deletion of the native signal sequence, both the specific productivity (164.8 U/L/h) and volumetric activity (27 U/mL) increased more than 40-fold compared to the expression of myrosinase containing its native signal sequence in combination with α-mating factor. The deletion of the native signal sequence resulted in slight changes in myrosinase properties: the optimum pH shifted from 6.5 to 7.0 and the maximal activating concentration of ascorbic acid increased from 1 mM to 1.5 mM. Kinetic parameters toward sinigrin were determined: 0.249 mM (K_m) and 435.7 U/mg (V_max). These results could be applied to the expression of other plant enzymes.

Mitochondrial permeability transition pores (mPTPs) have become an important topic in investigating the initiation and signaling pathways involved in cardioprotection. Experimental streptozotocin-induced diabetes mellitus (D) was shown to provide sufficient protection to the myocardium via compensatory mechanisms enabling mitochondria to produce energy under pathological conditions during the acute phase. The hypothesized involvement of mPTPs in these processes prompted us to use liquid chromatography and mass spectrometry-based proteomic analysis to investigate the effects of the acute-phase D condition on the structural and regulatory components of this multienzyme complex and the changes caused by compensation events. We detected ADT1, ATP5H, ATPA, and ATPB as the most abundant mPTP proteins. The between-group differences in protein abundance of the mPTP complex as a whole were significantly upregulated in the D group when compared with the control (C) group (p = 0.0106), but fold changes in individual protein expression levels were not significantly altered except for ATP5H, ATP5J, and KCRS. However, none of them passed the criterion of a 1.5-fold change in differential expression for biologically meaningful change. Visualization of the (dis-)similarity between the C and D groups and pairwise correlations revealed different patterns of protein interactions under the C and D conditions which may be linked to endogenous protective processes, of which beneficial effects on myocardial function were previously confirmed.

Heart failure (HF) is a leading cause of morbidity and mortality, often driven by prolonged exposure to pathological stimuli such as pressure and volume overload. These factors contribute to excessive oxidative stress, adverse cardiac remodeling, and dysregulation of the nitric oxide‐soluble guanylate cyclase‐cyclic guanosine monophosphate (NO‐sGC‐cGMP) signaling pathway. Given the urgent need for effective treatments, this study investigated the potential of sGC stimulators to mitigate HF progression. We utilized male hypertensive Ren‐2 transgenic (TGR) rats and a volume‐overload HF model induced by an aortocaval fistula (ACF). Rats received the sGC stimulator BAY 41–8543 (3 mg/kg/day) for 30 weeks, while normotensive Hannover Sprague–Dawley rats served as controls. At the study endpoint (40 weeks of age), left ventricular tissue was analyzed using mass spectrometry, Western blotting, and histological assessment. TGR rats treated with sGC stimulators exhibited a significant increase in key antioxidant proteins (SOD1, CH10, ACSF2, NDUS1, DHE3, GSTM2, and PCCA), suggesting enhanced resistance to oxidative stress. However, sGC stimulator treatment also upregulated extracellular matrix remodeling markers (MMP‐2, TGF‐β, and SMAD2/3), which are typically associated with fibrosis. Despite this, Masson's trichrome staining revealed reduced collagen deposition in both TGR and TGR‐ACF rats receiving sGC stimulators. Notably, all untreated TGR‐ACF rats succumbed before the study endpoint, preventing direct assessment of sGC stimulator effects in advanced HF. These findings highlight the therapeutic potential of sGC stimulators in HF, particularly through their antioxidant effects. However, their concurrent influence on fibrosis warrants further investigation to optimize treatment strategies.

Background: Mitochondria play a central role in cardiac energy metabolism and dynamically adapt to changes in metabolic demand. However, the early mitochondrial adaptations accompanying the acute phase of diabetes mellitus remain insufficiently understood. This study aimed to characterise diabetes-induced mitochondrial remodelling in the rat heart. Methods: Diabetes was induced using an established streptozotocin-induced rat model. Cardiac mitochondrial proteomes were analyzed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) in control and diabetic animals. Differential protein abundance was assessed by statistical comparison between groups using the limma package in R, and machine learning classification was used to identify proteins with the strongest discriminatory power between control and diabetic states. Results: Diabetes was associated with distinct mitochondrial proteomic remodelling. In the diabetic group, monoamine oxidase A (AOFA, padjust = 0.003) was markedly upregulated, fatty acid β-oxidation-related enzymes including dienoyl-CoA isomerase (ECH1, padjust < 0.001) and dienoyl-CoA reductase (DECR, padjust = 0.003) showed increased abundance, and respiratory chain complex I components, particularly NADH-ubiquinone oxidoreductase 75 kDa subunit (NDUS1, padjust = 0.016) and NADH dehydrogenase [ubiquinone] iron-sulfur protein 2 (NDUS2, padjust = 0.016), were elevated. Machine learning analysis consistently identified AOFA and key metabolic proteins as the strongest discriminators between diabetic and control animals (n = 6 per group). These changes indicate a coordinated shift towards enhanced lipid utilisation, altered mitochondrial respiratory function, and involvement of redox-associated processes. Conclusions: The observed proteomic changes may reflect early adaptive and compensatory mechanisms supporting mitochondrial function under increased energetic and oxidative load and highlight pathways that may represent promising candidates for targeted therapeutic modulation in diabetic cardiac dysfunction.