Department Of Human Genetics And Molecular Medicine
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Item Targeting dynamin-related protein-1 as a potential therapeutic approach for mitochondrial dysfunction in Alzheimer's disease(Elsevier B.V., 2023-06-29T00:00:00) Bhatti, Jasvinder Singh; Kaur, Satinder; Mishra, Jayapriya; Dibbanti, Harikrishnareddy; Singh, Arti; Reddy, Arubala P.; Bhatti, Gurjit Kaur; Reddy, P. HemachandraAlzheimer's disease (AD) is a neurodegenerative disease that manifests its pathology through synaptic damage, mitochondrial abnormalities, microRNA deregulation, hormonal imbalance, increased astrocytes & microglia, accumulation of amyloid ? (A?) and phosphorylated Tau in the brains of AD patients. Despite extensive research, the effective treatment of AD is still unknown. Tau hyperphosphorylation and mitochondrial abnormalities are involved in the loss of synapses, defective axonal transport and cognitive decline in patients with AD. Mitochondrial dysfunction is evidenced by enhanced mitochondrial fragmentation, impaired mitochondrial dynamics, mitochondrial biogenesis and defective mitophagy in AD. Hence, targeting mitochondrial proteins might be a promising therapeutic strategy in treating AD. Recently, dynamin-related protein 1 (Drp1), a mitochondrial fission protein, has gained attention due to its interactions with A? and hyperphosphorylated Tau, altering mitochondrial morphology, dynamics, and bioenergetics. These interactions affect ATP production in mitochondria. A reduction in Drp1 GTPase activity protects against neurodegeneration in AD models. This article provides a comprehensive overview of Drp1's involvement in oxidative damage, apoptosis, mitophagy, and axonal transport of mitochondria. We also highlighted the interaction of Drp1 with A? and Tau, which may contribute to AD progression. In conclusion, targeting Drp1 could be a potential therapeutic approach for preventing AD pathology. � 2023Item Oncogenic metabolic reprogramming in breast cancer: focus on signaling pathways and mitochondrial genes(Springer, 2023-05-11T00:00:00) Malayil, Rhuthuparna; Chhichholiya, Yogita; Vasudeva, Kanika; Singh, Harsh Vikram; Singh, Tashvinder; Singh, Sandeep; Munshi, AnjanaOncogenic metabolic reprogramming impacts the abundance of key metabolites that regulate signaling and epigenetics. Metabolic vulnerability in the cancer cell is evident from the Warburg effect. The research on metabolism in the progression and survival of breast cancer (BC) is under focus. Oncogenic signal activation and loss of�tumor suppressor are important regulators of tumor cell metabolism. Several intrinsic and extrinsic factors contribute to metabolic reprogramming. The molecular mechanisms underpinning metabolic reprogramming in BC are extensive and only partially defined. Various signaling pathways involved in the metabolism play a significant role in the modulation of BC. Notably, PI3K/AKT/mTOR pathway, lactate-ERK/STAT3 signaling, loss of the tumor suppressor Ras, Myc, oxidative stress, activation of the cellular hypoxic response and acidosis contribute to different metabolic reprogramming phenotypes linked to enhanced glycolysis. The alterations in mitochondrial genes have also been elaborated upon along with their functional implications. The outcome of these active research areas might contribute to the development of novel therapeutic interventions and the remodeling of known�drugs. � 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.Item Let-7a induces metabolic reprogramming in breast cancer cells via targeting mitochondrial encoded ND4(BioMed Central Ltd, 2021-11-27T00:00:00) Sharma, Praveen; Sharma, Vibhuti; Ahluwalia, Tarunveer Singh; Dogra, Nilambra; Kumar, Santosh; Singh, SandeepBackground and objectives: MicroRNA (miRNA) that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNA (mitomiR). Albeit mitomiRs have been shown to modulate gene expression, their functional impact within mitochondria is unknown. The main objective of this study is to investigate whether the mitochondrial genome is regulated by miR present inside the mitochondria. Methods and results: Here, we report mitomiR let-7a regulates mitochondrial transcription in breast cancer cells and reprogram the metabolism accordingly. These effects were mediated through the interaction of let-7a with mtDNA, as studied by RNA pull-down assays, altering the activity of Complex I in a cell line-specific manner. Our study, for the first time, identifies the role of mitomiR (let-7a) in regulating the mitochondrial genome by transcriptional repression and its contribution to regulating mitochondrial metabolism of breast cancer cells. Conclusion: These findings uncover a novel mechanism by which mitomiR regulates mitochondrial transcription. � 2021, The Author(s).Item Small regulatory molecules acting big in cancer: Potential role of mito-miRs in cancer(Bentham Science Publishers, 2019) Sharma P.; Bharat; Dogra N.; Singh S.MicroRNAs [miRNAs] are short, non-coding, single stranded RNA molecules regulating gene expression of their targets at the posttranscriptional level by either degrading mRNA or by inhibiting translation. Previously, miRNAs have been reported to be present inside the mitochondria and these miRNAs have been termed as mito-miRs. Origin of these mito-miRs may either be from mitochondrial genome or import from nucleus. The second class of mito-miRs makes it important to unravel the involvement of miRNAs in crosstalk between nucleus and mitochondria. Since miRNAs are involved in various physiological processes, their deregulation is often associated with disease progression, including cancer. The current review focuses on the involvement of miRNAs in different mitochondrial mediated processes. It also highlights the importance of exploring the interaction of miRNAs with mitochondrial genome, which may lead to the development of small regulatory RNA based therapeutic options.