bims-cemest Biomed News
on Cell metabolism and stress
Issue of 2025–01–26
eight papers selected by
Jessica Rosarda, Uniformed Services University
  1. Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies.
  2. Mitochondrial quality control: Biochemical mechanism of cardiovascular disease.
  3. MitoStores: stress-induced aggregation of mitochondrial proteins.
  4. Key Role of Phosphorylation in Small Heat Shock Protein Regulation via Oligomeric Disaggregation and Functional Activation.
  5. Mitochondrial protein import stress.
  6. Inter-organ metabolic interaction networks in non-alcoholic fatty liver disease.
  7. Bypassing senescence.
  8. Bioinformatics analysis and alternative polyadenylation in Heat Shock Proteins 70 (HSP70) family members.
  1. Neurotherapeutics. 2025 Jan 17. pii: S1878-7479(25)00003-0. [Epub ahead of print] e00525
    Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies.
    Kyle C McGill Percy, Zhunren Liu, Xin Qi.
      Alzheimer's disease (AD) is characterized by progressive neurodegeneration, marked by the accumulation of amyloid-β (Aβ) plaques and tau tangles. Emerging evidence suggests that mitochondrial dysfunction plays a pivotal role in AD pathogenesis, driven by impairments in mitochondrial quality control (MQC) mechanisms. MQC is crucial for maintaining mitochondrial integrity through processes such as proteostasis, mitochondrial dynamics, mitophagy, and precise communication with other subcellular organelles. In AD, disruptions in these processes lead to bioenergetic failure, gene dysregulation, the accumulation of damaged mitochondria, neuroinflammation, and lipid homeostasis impairment, further exacerbating neurodegeneration. This review elucidates the molecular pathways involved in MQC and their pathological relevance in AD, highlighting recent discoveries related to mitochondrial mechanisms underlying neurodegeneration. Furthermore, we explore potential therapeutic strategies targeting mitochondrial dysfunction, including gene therapy and pharmacological interventions, offering new avenues for slowing AD progression. The complex interplay between mitochondrial health and neurodegeneration underscores the need for innovative approaches to restore mitochondrial function and mitigate the onset and progression of AD.
    Keywords:  Alzheimer's disease; Amyloid beta; Gene therapy; Mitochondrial quality control; Pharmacotherapy; Tauopathy
    DOI:  https://doi.org/10.1016/j.neurot.2025.e00525
  2. Biochim Biophys Acta Mol Cell Res. 2025 Jan 19. pii: S0167-4889(25)00011-4. [Epub ahead of print]1872(3): 119906
    Mitochondrial quality control: Biochemical mechanism of cardiovascular disease.
    Francesca Inferrera, Ylenia Marino, Tiziana Genovese, Salvatore Cuzzocrea, Roberta Fusco, Rosanna Di Paola.
      Mitochondria play a key role in the regulation of energy homeostasis and ATP production in cardiac cells. Mitochondrial dysfunction can trigger several pathological events that contribute to the development and progression of cardiovascular diseases. These mechanisms include the induction of oxidative stress, dysregulation of intracellular calcium cycling, activation of the apoptotic pathway, and alteration of lipid metabolism. This review focuses on the role of mitochondria in intracellular signaling associated with cardiovascular diseases, emphasizing the contributions of reactive oxygen species production and mitochondrial dynamics. Indeed, mitochondrial dysfunction has been implicated in every aspect of cardiovascular disease and is currently being evaluated as a potential target for therapeutic interventions. To treat cardiovascular diseases and improve overall heart health, it is important to better understand these biochemical systems. These findings allow the achievement of targeted therapies and preventive measures. Therefore, this review investigates different studies that demonstrate how changes in mitochondrial dynamics like fusion, fission, and mitophagy contribute to the development or worsening of disorders related to heart diseases by summarizing current research on their role.
    Keywords:  Cardiovascular diseases; Intracellular signaling; Mitochondrial dysfunction; Oxidative stress; Therapeutic interventions
    DOI:  https://doi.org/10.1016/j.bbamcr.2025.119906
  3. Biol Chem. 2025 Jan 21.
    MitoStores: stress-induced aggregation of mitochondrial proteins.
    Pragya Kaushik, Johannes M Herrmann, Katja G Hansen.
      Most mitochondrial proteins are synthesized in the cytosol and post-translationally imported into mitochondria. If the rate of protein synthesis exceeds the capacity of the mitochondrial import machinery, precursor proteins can transiently accumulate in the cytosol. The cytosolic accumulation of mitochondrial precursors jeopardizes cellular protein homeostasis (proteostasis) and can be the cause of diseases. In order to prevent these toxic effects, most non-imported precursors are rapidly degraded by the ubiquitin-proteasome system. However, cells employ a second layer of defense which is the facilitated sequestration of mitochondrial precursor proteins in transient protein aggregates. The formation of such structures is triggered by nucleation factors such as small heat shock proteins. Disaggregases and chaperones can liberate precursors from cytosolic aggregates to pass them on to the mitochondrial import machinery or, under persistent stress conditions, to the proteasome for degradation. Owing to their role as transient buffering systems, these aggregates were referred to as MitoStores. This review articles provides a general overview about the MitoStore concept and the early stages in mitochondrial protein biogenesis in yeast and, in cases where aspects differ, in mammalian cells.
    Keywords:  aggregates; mitochondria; mitostores; proteasome; protein targeting; quality control
    DOI:  https://doi.org/10.1515/hsz-2024-0148
  4. Cells. 2025 Jan 17. pii: 127. [Epub ahead of print]14(2):
    Key Role of Phosphorylation in Small Heat Shock Protein Regulation via Oligomeric Disaggregation and Functional Activation.
    Zachary B Sluzala, Angelina Hamati, Patrice E Fort.
      Heat shock proteins (HSPs) are essential molecular chaperones that protect cells by aiding in protein folding and preventing aggregation under stress conditions. Small heat shock proteins (sHSPs), which include members from HSPB1 to HSPB10, are particularly important for cellular stress responses. These proteins share a conserved α-crystallin domain (ACD) critical for their chaperone function, with flexible N- and C-terminal extensions that facilitate oligomer formation. Phosphorylation, a key post-translational modification (PTM), plays a dynamic role in regulating sHSP structure, oligomeric state, stability, and chaperone function. Unlike other PTMs such as deamidation, oxidation, and glycation-which are often linked to protein destabilization-phosphorylation generally induces structural transitions that enhance sHSP activity. Specifically, phosphorylation promotes the disaggregation of sHSP oligomers into smaller, more active complexes, thereby increasing their efficiency. This disaggregation mechanism is crucial for protecting cells from stress-induced damage, including apoptosis, inflammation, and other forms of cellular dysfunction. This review explores the role of phosphorylation in modulating the function of sHSPs, particularly HSPB1, HSPB4, and HSPB5, and discusses how these modifications influence their protective functions in cellular stress responses.
    Keywords:  HSPB1; HSPB4; HSPB5; PTM; phosphorylation; post-translational modification; sHSP; αA-crystallin; αB-crystallin
    DOI:  https://doi.org/10.3390/cells14020127
  5. Nat Cell Biol. 2025 Jan 22.
    Mitochondrial protein import stress.
    Nikolaus Pfanner, Fabian den Brave, Thomas Becker.
      Mitochondria have to import a large number of precursor proteins from the cytosol. Chaperones keep these proteins in a largely unfolded state and guide them to the mitochondrial import sites. Premature folding, mitochondrial stress and import defects can cause clogging of import sites and accumulation of non-imported precursors, representing a critical burden for cellular proteostasis. Here we discuss how cells respond to mitochondrial protein import stress by regenerating clogged import sites and inducing stress responses. The mitochondrial protein import machinery has a dual role by serving as sensor for detecting mitochondrial dysfunction and inducing stress-response pathways. The production of chaperones that fold or sequester precursor proteins in deposits is induced and the proteasomal activity is increased to remove the excess precursor proteins. Together, these pathways reveal how mitochondria are tightly integrated into a cellular proteostasis and stress response network to maintain cell viability.
    DOI:  https://doi.org/10.1038/s41556-024-01590-w
  6. Front Endocrinol (Lausanne). 2024 ;15 1494560
    Inter-organ metabolic interaction networks in non-alcoholic fatty liver disease.
    Yu-Hong Fan, Siyao Zhang, Ye Wang, Hongni Wang, Hongliang Li, Lan Bai.
      Non-alcoholic fatty liver disease (NAFLD) is a multisystem metabolic disorder, marked by abnormal lipid accumulation and intricate inter-organ interactions, which contribute to systemic metabolic imbalances. NAFLD may progress through several stages, including simple steatosis (NAFL), non-alcoholic steatohepatitis (NASH), cirrhosis, and potentially liver cancer. This disease is closely associated with metabolic disorders driven by overnutrition, with key pathological processes including lipid dysregulation, impaired lipid autophagy, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and local inflammation. While hepatic lipid metabolism in NAFLD is well-documented, further research into inter-organ communication mechanisms is crucial for a deeper understanding of NAFLD progression. This review delves into intrahepatic networks and tissue-specific signaling mediators involved in NAFLD pathogenesis, emphasizing their impact on distal organs.
    Keywords:  Inter-organ crosstalk; endoplasmic reticulum (ER) stress; fatty acid synthesis; mitochondrial homeostasis; non-alcoholic fatty liver disease
    DOI:  https://doi.org/10.3389/fendo.2024.1494560
  7. Sci Signal. 2025 Jan 21. 18(870): eadv9441
    Bypassing senescence.
    Annalisa M VanHook.
      A metabolic switch enables hepatocytes in damaged livers to escape senescence and form tumors.
    DOI:  https://doi.org/10.1126/scisignal.adv9441
  8. Int J Physiol Pathophysiol Pharmacol. 2024 ;16(6): 138-151
    Bioinformatics analysis and alternative polyadenylation in Heat Shock Proteins 70 (HSP70) family members.
    Srishti Shriya, Ramakrushna Paul, Neha Singh, Farhat Afza, Buddhi Prakash Jain.
       OBJECTIVE: The Heat Shock Protein 70 (HSP70) family is a highly conserved group of molecular chaperones essential for maintaining cellular homeostasis. These proteins are necessary for protein folding, assembly, and degradation and involve cell recovery from stress conditions. HSP70 proteins are upregulated in response to heat shock, oxidative stress, and pathogenic infections. Their primary role is preventing protein aggregation, refolding misfolded proteins, and targeted degradation of irreparably damaged proteins. Given their involvement in fundamental cellular processes and stress responses, HSP70 proteins are critical for cell survival and modulating disease outcomes in cancer, neurodegeneration, and other pathologies. The present study aims to understand domain architecture, physicochemical properties, phosphorylation, ubiquitination, and alternative polyadenylation site prediction in various HSP70 members.
    METHOD: SMART and InterProScan software were used for domain analysis. EXPASY Protparam, NetPhos 3.1 server DTU, and MUbisiDa were used for physicochemical analysis, phosphorylation, and ubiquitination site analysis, respectively. Alternative polyadenylation was studied using the EST database.
    RESULT: Domain analysis shows that coiled-coil and nucleotide-binding domains are present in some of the HSP70 members. Five HSP70 family members have alternate polyadenylation sites in their 3'UTR.
    CONCLUSION: The present work has provided valuable insights into their structure, functions, interactome, and polyadenylation patterns. Studying their therapeutic potential in diseases like cancer can be helpful.
    Keywords:  Heat Shock Protein; alternative polyadenylation; chaperones; domain; protein folding
    DOI:  https://doi.org/10.62347/CWPE7813
This page is being maintained by Thomas Krichel. It was last updated on 2025‒04‒10 at 16:45.