bims-metalz 2024-03-17 papers

Issue of 2024–03–17
four papers selected by
Mikaila Chetty, Goa University

J Appl Toxicol. 2024 Mar 12.

CYP14 family in Caenorhabditis elegans: Mitochondrial function, detoxification, and lifespan.

Sharoen Yu Ming Lim, Yan Pan, Mustafa Alshagga, Willone Lim, Kong Cin, Salah A Alshehade, Mohammed Alshawsh.

CYP-14 members of the Caenorhabditis elegans (C. elegans) Cytochrome P450 (CYP) enzyme family, plays important roles in mitochondrial dysfunction, detoxification, lipid metabolism, defense and lifespan regulation. The review identifies CYP-14 members: cyp-14A1, cyp-14A2, cyp-14A3, cyp-14A4, cyp-14A5 and their homology with human CYP families. Despite limited studies on C. elegans cyp-14 members, the findings unraveled their complex crosstalk between mitochondrial stress, detoxification mechanisms, and lifespan regulation, emphasizing the complexity of these interconnected pathways as well as how their regulation depends on environmental cues changes including pH, nutrients, ROS and chemical stressors. The review underscores the translational relevance to human health, shedding light on potential human homologues and their implications in age-related, metabolic and respiratory diseases. Among other genes, cyp-14A2 and cyp-14A4 predominate the mitochondrial function, heat resistance, lipid metabolism, detoxification and lifespan pathways. In conclusion, these insights pave the way for future research, offering promising avenues for therapeutic interventions targeting CYP-14 activity to address age-related diseases and promote healthy aging.

Keywords: C. elegans; age-related; cyp-14; cyp-14A; mitochondrial dysfunction

DOI: https://doi.org/10.1002/jat.4597

Food Funct. 2024 Mar 14.

Cyclocodon lancifolius fruit prolongs the lifespan of Caenorhabditis elegans via antioxidation and regulation of purine metabolism.

Yihan Liu, Xudong Zhang, Yan Wang, Jianxia Wang, Hua Wei, Cunli Zhang, Qiang Zhang.

Cyclocodon lancifolius fruit is a promising commercial fruit with antioxidant activity and is rich in polyphenolic compounds. In this study, the anti-aging activity of C. lancifolius fruit extract (CF) on Caenorhabditis elegans (C. elegans) was evaluated by observing the longevity, stress response, reproduction, oscillation, lipofuscin, and antioxidant enzymes of worms. Moreover, the effects and potential mechanisms of CF on delaying C. elegans senescence at the mRNA and metabolite levels were investigated. The results showed that CF treatment significantly increased the lifespan and stress resistance, decreased the levels of lipofuscin and reactive oxygen species (ROS), and improved the antioxidant system of C. elegans. The extension of the lifespan of C. elegans was remarkably correlated with the upregulation of mtl-1 and Hsp-16.2, along with the downregulation of age-1, daf-2, and akt-1. Metabolomics analysis revealed that purine metabolism is a key regulatory pathway for CF to exert anti-aging effects. The present study suggests that C. lancifolius fruit has potential for use as a functional food to enhance antioxidant capacity and delay aging.

DOI: https://doi.org/10.1039/d3fo02931j

Mol Neurobiol. 2024 Mar 14.

Pongamol Prevents Neurotoxicity via the Activation of MAPKs/Nrf2 Signaling Pathway in H2O2-Induced Neuronal PC12 Cells and Prolongs the Lifespan of Caenorhabditis elegans.

Shaojun Wu, Jie Miao, Susu Zhu, Xinyuan Wu, Jindan Shi, Jichao Zhou, Yi Xing, Kun Hu, Jie Ren, Hao Yang.

Despite tremendous advances in modern medicine, effective prevention or therapeutic strategies for age-related neurodegenerative diseases such as Alzheimer's disease (AD) remain limited. Growing evidence now suggests that oxidative stress and apoptosis are increasingly associated with AD as promising therapeutic targets. Pongamol, a flavonoid, is the main constituent of pongamia pinnata and possesses a variety of pharmacological activities such as antioxidant, anti-aging and anti-inflammatory. In the present study, we investigated the antioxidant effects and mechanisms of pongamol in H2O2-induced PC12 cells and Caenorhabditis elegans (C. elegans). Our findings revealed that pongamol reduced cellular damage and apoptosis in H2O2-induced PC12 cells. Furthermore, pongamol reduced levels of apoptosis-related proteins Bax, Cyto C, Cleaved Caspase-3, and Cleaved PARP1, and increased the level of anti-apoptotic protein Bcl-2. Pongamol also effectively attenuated the level of oxidative stress markers such as glutathione (GSH) and reactive oxygen species (ROS) in H2O2-induced PC12 cells. Additionally, pongamol possessed antioxidant activity in H2O2-induced PC12 cells through the MAPKs/Nrf2 signaling pathway. Furthermore, pongamol exerted neuroprotective and anti-aging effects in C. elegans. All together, these results suggested that pongamol has a potential neuroprotective effect through the modulation of MAPKs/Nrf2 signaling pathway.

Keywords: Alzheimer’s disease; Apoptosis; MAPKs/Nrf2 signaling pathway; Oxidative stress; Pongamol

DOI: https://doi.org/10.1007/s12035-024-04110-x

Elife. 2024 Mar 14. pii: e92376. [Epub ahead of print]13

Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapses.

Rachel L Doser, Kaz M Knight, Ennis W Deihl, Frederic J Hoerndli.

Our understanding of mitochondrial signaling in the nervous system has been limited by the technical challenge of analyzing mitochondrial function in vivo. In the transparent genetic model Caenorhabditis elegans, we were able to manipulate and measure mitochondrial ROS (reactive oxygen species) signaling of individual mitochondria as well as neuronal activity of single neurons in vivo. Using this approach, we provide evidence supporting a novel role for mitochondrial ROS signaling in dendrites of excitatory glutamatergic C. elegans interneurons. Specifically, we show that following neuronal activity, dendritic mitochondria take up calcium (Ca2+) via the mitochondrial Ca2+ uniporter MCU-1 that results in an upregulation of mitochondrial ROS production. We also observed that mitochondria are positioned in close proximity to synaptic clusters of GLR-1, the C. elegans ortholog of the AMPA subtype of glutamate receptors that mediate neuronal excitation. We show that synaptic recruitment of GLR-1 is upregulated when MCU-1 function is pharmacologically or genetically impaired but is downregulated by mitoROS signaling. Thus, signaling from postsynaptic mitochondria may regulate excitatory synapse function to maintain neuronal homeostasis by preventing excitotoxicity and energy depletion.

Keywords: C. elegans; cell biology; neuroscience

DOI: https://doi.org/10.7554/eLife.92376