BAX mitochondrial integration is regulated allosterically by its α1−α2 loop

Dengler, Michael A.; Gibson, Leonie; Adams, Jerry M.

doi:10.1038/s41418-021-00815-x

Cited by 10 publications

(15 citation statements)

References 39 publications

(76 reference statements)

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“…90 Bax acts as a proapoptotic factor and has been confirmed to cause mitochondrial membrane depolarization and promote the release of apoptosis factors from mitochondria, leading to cell death. 91 The caspase family is downstream of the apoptosis pathway and is regulated by Bax. 92 Caspase 3 has been identified as one of the major executive caspase molecules during the process of apoptosis, 93 serving as a key enzyme in the mitochondria-dependent apoptosis pathway.…”

Section: Discussionmentioning

confidence: 99%

Effects of Dityrosine on Lactic Acid Metabolism in Mice Gastrocnemius Muscle During Endurance Exercise via the Oxidative Stress-Induced Mitochondria Damage

Xia,

Lan,

Pan

et al. 2024

J. Agric. Food Chem.

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Dityrosine (Dityr) has been detected in commercial food as a product of protein oxidation and has been shown to pose a threat to human health. This study aims to investigate whether Dityr causes a decrease in lactic acid metabolism in the gastrocnemius muscle during endurance exercise. C57BL/6 mice were administered Dityr or saline by gavage for 13 weeks and underwent an endurance exercise test on a treadmill. Dityr caused a severe reduction in motion displacement and endurance time, along with a significant increase in lactic acid accumulation in the blood and gastrocnemius muscle in mice after exercise. Dityr induced significant mitochondrial defects in the gastrocnemius muscle of mice. Additionally, Dityr induced serious oxidative stress in the gastrocnemius muscle, accompanied by inflammation, which might be one of the causes of mitochondrial dysfunction. Moreover, significant apoptosis in the gastrocnemius muscle increased after exposure to Dityr. This study confirmed that Dityr induced oxidative stress in the gastrocnemius muscle, which further caused significant mitochondrial damage in the gastrocnemius muscle cell, resulting in decreased capacity of lactic acid metabolism and finally affected performance in endurance exercise. This may be one of the possible mechanisms by which highly oxidized foods cause a decreased muscle energy metabolism.

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Section: Discussionmentioning

confidence: 99%

Effects of Dityrosine on Lactic Acid Metabolism in Mice Gastrocnemius Muscle During Endurance Exercise via the Oxidative Stress-Induced Mitochondria Damage

Xia,

Lan,

Pan

et al. 2024

J. Agric. Food Chem.

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“…The activated Bax migrates to the outer membrane of mitochondria by changing its morphology, thereby disrupting the integrity of the mitochondrial membrane. At the outer mitochondrial membrane, the Bax acts synergistically with Bcl-2, an inhibitor of apoptosis and an integrin of the mitochondrial membrane (Dengler et al, 2021). The Bax and Bcl-2 act as upstream regulatory mechanisms of caspase-3, which activates the caspses cascade and mediates apoptosis (Kulyar et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Excess Iron added to the diet induces the apoptosis of chicken’s liver through the PI3KAKT mTOR axis

Sun

et al. 2022

Preprint

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Iron (Fe), an essential trace element, plays a key role in biological metabolism. The PI3K/AKT/mTOR axis plays an important role in the control of apoptosis. However, the effect of iron overdose in the diet on the role of the PI3K/AKT/mTOR axis and apoptosis, and pathological liver damage in chickens are still poorly understood. In this study, 180 1-day-old chicks were divided into 3 groups, which were fed the basal diets supplemented with 50 (C), 500 (E1), and 1000 (E2) mg Fe/Kg as ferrous sulfate monohydrate (FeSO4·H2O) and returned to normal diet one day later, Tested on days 1, 3, 7, 14, and 21 after the end of the iron addition. The results showed that the liver morphology was normal in the group C. The groups E1 and E2 showed the structure destroyed of hepatic lobules, the disordered of hepatic cords, the reduction of the central veins and the presence of erythrocytes accompanied by inflammatory cell infiltration. The group E2 showed more serious damage than the group E1, but these phenomena will largely return to normal on day 21. The perls staining showed that large deposits of iron-containing hemosiderin in the hepatic sinus after iron overdose intake, and the changes of iron deposition and pathological damage had certain regularity in time. The expression of Bax, Caspase-3, Caspase-8, and Caspase-9 in groups E1 and E2 were increased from days 1 to 21, which was in contrast to the Bcl-2, and it has a dose dependent. This suggested that iron overdose triggered apoptosis, which was supported by our ultrastructural observations of chromatin marginalization and impaired mitochondrial swelling. In addition, the expression of PI3K and AKT were significantly increased in the iron overdose groups, while the expression of mTOR was decreased. Above all, iron overdose can induce apoptosis in chicken hepatocytes through regulation of the PI3K/AKT/mTOR axis, leading to pathological damage. The type of iron overdose-induced damage was dose-dependent but not permanent. These results provide a theoretical basis for a comprehensive understanding of the importance of mineral nutrition management in poultry and the possible risk of excessive iron intake.

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“…Distant recurrence rates still represent the leading cause of mortality for rectal cancer patients [ 18 ], thus affecting survival outcomes. The underlying molecular mechanisms are highly complex and seem to involve, for example, redox regulations [ 47 – 49 ], p53 family members [ 4 , 50 – 57 ], nucleic acid regulators [ 58 ], hypoxia regulators [ 59 ] or Bcle family members [ 60 – 63 ]. Distant disease control includes different long-term endpoints: disease free survival (DFS), overall survival (OS) and distant recurrence rate.…”

Section: Distant Disease Controlmentioning

confidence: 99%

Total neoadjuvant therapy for the treatment of locally advanced rectal cancer: a systematic minireview

et al. 2022

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Colorectal carcinoma is the second leading cause of cancer-related deaths, and indeed, rectal cancer accounting for approximately one third of newly diagnosed patients. Gold standard in the treatment of rectal cancer is a multimodality approach, aiming at a good control of the local disease. Distant recurrences are the major cause of mortality. Currently, Locally Advanced Rectal Cancer (LARC) patients undergo a combined treatment of chemotherapy and radiotherapy, followed by surgery. Eventually, more chemotherapy, namely adjuvant chemotherapy (aCT), may be necessary. Total Neoadjuvant Therapy (TNT) is an emerging approach aimed to reduce distant metastases and improve local control. Several ongoing studies are analyzing whether this new approach could improve oncological outcomes. Published results were encouraging, but the heterogeneity of protocols in use, makes the comparison and interpretation of data rather complex. One of the major concerns regarding TNT administration is related to its effect on larger and more advanced cancers that might not undergo similar down-staging as smaller, early-stage tumors. This minireview, based on a systematic literature search of randomized clinical trials and meta-analysis, summarizes current knowledge on TNT. The aim was to confirm or refute whether or not current practice of TNT is based on relevant evidence, to establish the quality of that evidence, and to address any uncertainty or variation in practice that may be occurring. A tentative grouping of general study characteristics, clinical features and treatments characteristics has been undertaken to evaluate if the reported studies are sufficiently homogeneous in terms of subjects involved, interventions, and outcomes to provide a meaningful idea of which patients are more likely to gain from this treatment.

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BAX mitochondrial integration is regulated allosterically by its α1−α2 loop

Cited by 10 publications

References 39 publications

Effects of Dityrosine on Lactic Acid Metabolism in Mice Gastrocnemius Muscle During Endurance Exercise via the Oxidative Stress-Induced Mitochondria Damage

Effects of Dityrosine on Lactic Acid Metabolism in Mice Gastrocnemius Muscle During Endurance Exercise via the Oxidative Stress-Induced Mitochondria Damage

Excess Iron added to the diet induces the apoptosis of chicken’s liver through the PI3KAKT mTOR axis

Total neoadjuvant therapy for the treatment of locally advanced rectal cancer: a systematic minireview

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