Lamprey PHB2 maintains mitochondrial stability by tanslocation to the mitochondria under oxidative stress

Wang

J Cellular Molecular Medi

2021

HCLS1-associated protein X-1 (HAX1), an anti-apoptotic molecular, overexpresses in glioma. However, the role of HAX1 in glioma cell surviving in hypoxic environment remains unclear. Western blotting, qRT-PCR, Transwell assay, TUNEL assay, wounding healing assay, clone formation, tumour xenograft model and immunohistochemical staining were used to investigate the role of HAX1 in glioma. HAX1 regulated by HIF-1α was increased in glioma cells cultured in hypoxia. Silencing of HAX1 could cause an increased apoptosis of glioma cells cultured in hypoxia. Silencing of HAX1 also decreased the proliferation, migration and invasion of glioma cells cultured in hypoxia. Increased mitochondrial fission could prevent glioma cells from the damage induced by HAX1 knockdown in hypoxia. Furthermore, HAX1 was found to regulate glioma cells through phosphorylated AKT/Drp signal pathway. In conclusion, our study suggested that HAX1 promoted survival of glioma cells in hypoxic environment via AKT/Drp signal pathway. Our study also provided a potential therapeutic target for glioma.

Section: Resultsmentioning

confidence: 99%

“…45,46 HAX1 is highly expressed in mitochondria, regulates mitochondrial metabolism and apoptosis induced by mitochondrial pathways. 21,50,51 Mito tracker assays showed that…”

Section: Hax1 Knockdown Decreases Mitochondrial Fission Of Glioma Cells Cultured In Hypoxiamentioning

confidence: 99%

HAX1 maintains the glioma progression in hypoxia through promoting mitochondrial fission

Wang

J Cellular Molecular Medi

2021

Oxidative Medicine and Cellular Longevity

“…The PHB2:S1P complex binds to cytochrome c oxidase, which is responsible for the correct assembly of the cytochrome c oxidase complex. Loss of PHB2 results in decreased mitochondrial HAX1 and activation of mitochondrial caspase 9/caspase 3, resulting in apoptosis [60].…”

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

Prohibitins: A Key Link between Mitochondria and Nervous System Diseases

Jiang

Wang

et al. 2022

Prohibitins (PHBs) are conserved proteins in eukaryotic cells, which are mainly located in the inner mitochondrial membrane (IMM), cell nucleus, and cell membrane. PHBs play crucial roles in various cellular functions, including the cell cycle regulation, tumor suppression, immunoglobulin M receptor binding, and aging. In addition, recent in vitro and in vivo studies have revealed that PHBs are important in nervous system diseases. PHBs can prevent apoptosis, inflammation, mitochondrial dysfunction, and autophagy in neurological disorders through different molecules and pathways, such as OPA-1, PINK1/Parkin, IL6/STAT3, Tau, NO, LC3, and TDP43. Therefore, PHBs show great promise in the protection of neurological disorders. This review summarizes the relevant studies on the relationship between PHBs and neurological disorders and provides an update on the molecular mechanisms of PHBs in nervous system diseases.

“…Its regulatory functions extend to mitochondrial morphology, membrane potential, and the assembly of respiratory chain complexes [21][22][23]. Additionally, PHB2 has been identified as a key player in modulating cellular responses to stress, including oxidative stress and apoptosis, through its impact on mitochondrial function [24,25]. Disruptions in PHB2 have been linked to mitochondrial dysfunction and the onset of various diseases, underscoring its significance in preserving mitochondrial health.…”

Section: Introductionmentioning

confidence: 99%

Pyruvate kinase M2 sustains cardiac mitochondrial integrity in septic cardiomyopathy by regulating PHB2-dependent mitochondrial biogenesis

Ren,

et al. 2024

Int. J. Med. Sci.

Previous studies have highlighted the protective effects of pyruvate kinase M2 (PKM2) overexpression in septic cardiomyopathy. In our study, we utilized cardiomyocyte-specific PKM2 knockout mice to further investigate the role of PKM2 in attenuating LPS-induced myocardial dysfunction, focusing on mitochondrial biogenesis and prohibitin 2 (PHB2). Our findings confirmed that the deletion of PKM2 in cardiomyocytes significantly exacerbated LPS-induced myocardial dysfunction, as evidenced by impaired contractile function and relaxation. Additionally, the deletion of PKM2 intensified LPS-induced myocardial inflammation. At the molecular level, LPS triggered mitochondrial dysfunction, characterized by reduced ATP production, compromised mitochondrial respiratory complex I/III activities, and increased ROS production. Intriguingly, the absence of PKM2 further worsened LPS-induced mitochondrial damage. Our molecular investigations revealed that LPS disrupted mitochondrial biogenesis in cardiomyocytes, a disruption that was exacerbated by the absence of PKM2. Given that PHB2 is known as a downstream effector of PKM2, we employed PHB2 adenovirus to restore PHB2 levels. The overexpression of PHB2 normalized mitochondrial biogenesis, restored mitochondrial integrity, and promoted mitochondrial function. Overall, our results underscore the critical role of PKM2 in regulating the progression of septic cardiomyopathy. PKM2 deficiency impeded mitochondrial biogenesis, leading to compromised mitochondrial integrity, increased myocardial inflammation, and impaired cardiac function. The overexpression of PHB2 mitigated the deleterious effects of PKM2 deletion. This discovery offers a novel insight into the molecular mechanisms underlying septic cardiomyopathy and suggests potential therapeutic targets for intervention.