bims-smemid Biomed News
on Stress metabolism in mitochondrial dysfunction
Issue of 2024‒06‒02
three papers selected by
Deepti Mudartha, The International Institute of Molecular Mechanisms and Machines
  1. ISR pathway contribution to tissue specificity of mitochondrial diseases.
  2. [Research progress in the regulation of autophagy and mitochondrial homeostasis by AMPK signaling channels].
  3. Regulation of eukaryotic transcription initiation in response to cellular stress.
  1. Trends Endocrinol Metab. 2024 May 27. pii: S1043-2760(24)00119-X. [Epub ahead of print]
    ISR pathway contribution to tissue specificity of mitochondrial diseases.
    Ana Vela-Sebastián, Pilar Bayona-Bafaluy, David Pacheu-Grau.
      Mitochondrial genetic defects caused by whole-body mutations typically affect different tissues in different ways. Elucidating the molecular determinants that cause certain cell types to be primarily affected has become a critical research target within the field. We propose a differential activation of the integrated stress response as a potential contributor to this tissue specificity.
    DOI:  https://doi.org/10.1016/j.tem.2024.05.001
  2. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2024 Apr;36(4): 425-429
    [Research progress in the regulation of autophagy and mitochondrial homeostasis by AMPK signaling channels].
    Peisen Ruan, Yao Zheng, Zhuoya Dong, Yan Wang, Ya'nan Xu, Hehe Chen.
      AMP-activated protein kinase (AMPK) is a widely distributed and evolutionarily conserved serine/threonine protein kinase present in eukaryotic cells. In regulating cellular energy metabolism, AMPK plays an extremely important role as an energy metabolic kinase. When the body is in a low energy state, AMPK is activated in response to changes in intracellular adenine nucleotide levels and is bound to adenosine monophosphate (AMP) or adenosine diphosphate (ADP). Activated AMPK regulates various metabolic processes, including lipid and glucose metabolism and cellular autophagy. AMPK directly promotes autophagy by phosphorylating autophagy-related proteins in the mammalian target of rapamycin complex 1 (mTORC1), serine/threonine protein kinase-dysregulated 51-like kinase 1 (ULK1) and type III phosphatidylinositol 3-kinase-vacuolar protein-sorting 34 (PIK3C3-VPS34) complexes. AMPK also indirectly promotes autophagy by regulating the expression of downstream autophagy-related genes of transcription factors such as forkhead box O3 (FOXO3), lysosomal function transcription factor EB (TFEB) and bromodomain protein 4 (BRD4). AMPK also regulates mitochondrial autophagy, induces the division of damaged mitochondria and promotes the transfer of the autophagic response to damaged mitochondria. Another function of AMPK is to regulate mitochondrial health by stimulating mitochondrial biogenesis and participating in various aspects of mitochondrial homeostasis regulation. This review discusses the specific regulation of mitochondrial biology and internal environmental homeostasis by AMPK signaling channels as central to the cellular response to energy stress and regulation of mitochondria, highlighting the key role of AMPK in regulating cellular autophagy and mitochondrial autophagy, as well as advances in research on the regulation of mitochondrial homeostasis.
    DOI:  https://doi.org/10.3760/cma.j.cn121430-20230302-00132
  3. Gene. 2024 May 23. pii: S0378-1119(24)00497-9. [Epub ahead of print]924 148616
    Regulation of eukaryotic transcription initiation in response to cellular stress.
    Jannatul Ferdoush, Rizwaan Abdul Kadir, Matthew Ogle, Ayan Saha.
      Transcription initiation is a vital step in the regulation of eukaryotic gene expression. It can be dysregulated in response to various cellular stressors which is associated with numerous human diseases including cancer. Transcription initiation is facilitated via many gene-specific trans-regulatory elements such as transcription factors, activators, and coactivators through their interactions with transcription pre-initiation complex (PIC). These trans-regulatory elements can uniquely facilitate PIC formation (hence, transcription initiation) in response to cellular nutrient stress. Cellular nutrient stress also regulates the activity of other pathways such as target of rapamycin (TOR) pathway. TOR pathway exhibits distinct regulatory mechanisms of transcriptional activation in response to stress. Like TOR pathway, the cell cycle regulatory pathway is also found to be linked to transcriptional regulation in response to cellular stress. Several transcription factors such as p53, C/EBP Homologous Protein (CHOP), activating transcription factor 6 (ATF6α), E2F, transforming growth factor (TGF)-β, Adenomatous polyposis coli (APC), SMAD, and MYC have been implicated in regulation of transcription of target genes involved in cell cycle progression, apoptosis, and DNA damage repair pathways. Additionally, cellular metabolic and oxidative stressors have been found to regulate the activity of long non-coding RNAs (lncRNA). LncRNA regulates transcription by upregulating or downregulating the transcription regulatory proteins involved in metabolic and cell signaling pathways. Numerous human diseases, triggered by chronic cellular stressors, are associated with abnormal regulation of transcription. Hence, understanding these mechanisms would help unravel the molecular regulatory insights with potential therapeutic interventions. Therefore, here we emphasize the recent advances of regulation of eukaryotic transcription initiation in response to cellular stress.
    Keywords:  ATF6α; CHOP; Cellular Stress; E2F; P53; RNA Pol II; SAGA; TFIID; TOR; Transcription initiation; lncRNA
    DOI:  https://doi.org/10.1016/j.gene.2024.148616
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