The lumen of the endoplasmic reticulum (ER) is usually considered an oxidative environment; however, oxidized thiol-disulfides and reduced pyridine nucleotides occur there parallelly, indicating that the ER lumen lacks components which connect the two systems. Here, we investigated the luminal presence of the thioredoxin (Trx)/thioredoxin reductase (TrxR) proteins, capable of linking the protein thiol and pyridine nucleotide pools in different compartments. It was shown that specific activity of TrxR in the ER is undetectable, whereas higher activities were measured in the cytoplasm and mitochondria. None of the Trx/TrxR isoforms were expressed in the ER by Western blot analysis. Co-localization studies of various isoforms of Trx and TrxR with ER marker Grp94 by immunofluorescent analysis further confirmed their absence from the lumen. The probability of luminal localization of each isoform was also predicted to be very low by several in silico analysis tools. ER-targeted transient transfection of HeLa cells with Trx1 and TrxR1 significantly decreased cell viability and induced apoptotic cell death. In conclusion, the absence of this electron transfer chain may explain the uncoupling of the redox systems in the ER lumen, allowing parallel presence of a reduced pyridine nucleotide and a probably oxidized protein pool necessary for cellular viability.

Helicobacter pylori (H. pylori) infection is one of the most common bacterial infections worldwide. Its role in infection-associated cancers, such as gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma is well known. However, mitochondrial alterations in these malignancies are less documented. Mitochondria are key organelles, maintaining cellular homeostasis under normal and pathological conditions. They regulate complex cellular processes and play a key role in carcinogenesis and cancer progression in H. pylori-associated malignancies. This review summarizes the role of mitochondrial stress in H. pylori infection, gastric cancer, and MALT lymphoma.

Epithelial ovarian cancer is one of the most lethal gynecological malignancies worldwide. Its development strongly depends on several genetic and environmental factors, with metabolic components and cellular redox homeostasis alterations playing a significant a role in its development and disease progression. In this review, we summarize the contribution of mitochondrial and endoplasmic reticulum (ER) stress in the pathogenesis of epithelial ovarian cancer along with their role as potential biomarkers and therapeutic targets, including proteins of glucose metabolism, mitochondrial fission and fusion, mitophagy, membrane-associated ring-CH-type finger 5 (MARCH5), A-kinase anchoring proteins (AKAPs), proteins regulating mitochondrial Ca²⁺ homeostasis, mitochondrial unfolded protein response (UPRmt) proteins, activating transcription factors (ATFs), CCAAT enhancer binding protein (C/EBP) homologous protein (CHOP), ‘mitokines’, GRP75, and GRP78. Although many of these potential targets are in preclinical phase, they have a high potential to become valuable alternative or additive treatments for epithelial ovarian cancers.

Helicobacter pylori (H. pylori) infection is recognized as one of the most common bacterial infections worldwide. Its role in infection-associated cancers, such as in gastric cancer and MALT-lymphoma, is well known. Mitochondrial alterations in these malignancies are less documented. Mitochondria is a key organelle in maintaining cellular homeostasis under normal and pathological conditions. They regulate complex cellular processes, and they are key players in carcinogenesis and cancer progression in these H.pylori-associated malignancies. In this review, we summarize the role of mitochondrial stress in H. pylori infection, in gastric cancer, and MALT-lymphoma.