Short Communication - Journal of Cell Biology and Metabolism (2023) Volume 5, Issue 3
Molecular mechanisms of metabolic rewiring in cancer cells and therapeutic implications.
Department of Genetics, Stanford University, Stanford, CA 94305, USA
- *Corresponding Author:
- Folmes Wanet
Department of Genetics
Stanford, CA 94305, USA
Received:23-May-2023,Manuscript No. AACBM-23-101827; Editor assigned: 26-May-2023, PreQC No. AACBM-23-101827(PQ); Reviewed:09-Jun-2023, QC No. AACBM-23-101827; Revised:13-Jun-2023, Manuscript No. AACBM-23-101827(R); Published:21-Jun-2023, DOI: 10.35841/aacbm- 5.3.153
Citation: Wanet F. Metabolic coordination and organelle communication from a cellular perspective. J Cell Biol Metab. 2023; 5(3):153
Cells are intricate systems with numerous organelles working together to maintain homeostasis and ensure proper cellular function. Metabolic coordination and organelle communication play pivotal roles in cellular physiology, allowing cells to respond to changing energy demands, nutrient availability, and stress conditions. This article explores the mechanisms by which cells coordinate metabolic processes and communicate between organelles, highlighting their importance in cellular function and their implications in health and disease.
Metabolic pathways and interplay
Cells employ a network of interconnected metabolic pathways to generate energy, synthesize macromolecules, and maintain essential cellular functions. These pathways include glycolysis, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, fatty acid oxidation, and amino acid metabolism, among others. While each pathway serves distinct purposes, they are tightly interconnected and functionally interdependent. Metabolic coordination involves the regulation of these interconnected pathways to ensure energy and substrate availability for specific cellular needs. Key regulators, such as hormones and cellular energy sensors, monitor nutrient availability and energy status and orchestrate metabolic responses accordingly. For example, the hormone insulin regulates glucose metabolism by stimulating glucose uptake and glycogen synthesis in response to high blood glucose levels. Metabolic coordination is also achieved through substrate channeling, where intermediates of one metabolic pathway are directly transferred to another pathway without fully entering the cytoplasm. This process minimizes the loss of intermediates and enhances metabolic efficiency. An example of substrate channeling is the direct transfer of reducing equivalents from glycolysis to the electron transport chain in mitochondria via the malate-aspartate shuttle.
Organelle communication in cellular metabolism
Cells comprise various organelles, including the nucleus, endoplasmic reticulum (ER), mitochondria, peroxisomes, and lysosomes, among others. Efficient communication between these organelles is crucial for maintaining cellular homeostasis and coordinating metabolic processes. Several mechanisms facilitate organelle communication, enabling the exchange of signals and metabolites. One prominent example of organelle communication is the cross-talk between the nucleus and other organelles. The nucleus houses the genome and regulates gene expression, allowing cells to respond to metabolic cues. Transcription factors, such as peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), play a key role in coordinating nuclear gene expression with mitochondrial biogenesis and oxidative metabolism. Mitochondria, often referred to as the powerhouse of the cell, are crucial for energy metabolism and are involved in various signaling pathways. Mitochondrial dynamics, including fusion and fission, allow for efficient exchange of metabolites, proteins, and genetic material. Additionally, mitochondria communicate with the ER through contact sites known as mitochondria-associated ER membranes (MAMs). MAMs facilitate the exchange of lipids, calcium ions, and other signaling molecules, influencing processes such as ER stress response and lipid metabolism.
The ER, an interconnected network of membranes, is involved in protein synthesis, lipid synthesis, and calcium homeostasis. The ER communicates with other organelles through membrane contact sites, including MAMs with mitochondria and specialized sites with peroxisomes and lysosomes. ER stress, caused by the accumulation of misfolded proteins, triggers the unfolded protein response (UPR) to restore ER homeostasis. The UPR involves communication between the ER and the nucleus to regulate gene expression and enhance protein folding capacity. Peroxisomes and lysosomes are essential for cellular metabolism and degradation processes. Peroxisomes are involved in fatty acid oxidation and detoxification reactions, while lysosomes are responsible for intracellular degradation and recycling. The interaction between peroxisomes and mitochondria contributes to lipid metabolism and energy production. Lysosomes communicate with other organelles through vesicular transport, allowing the delivery of substrates for degradation and the recycling of macromolecules.
Implications in health and disease
Disruptions in metabolic coordination and organelle communication can have profound implications for cellular function and contribute to various diseases. Dysregulation of metabolic pathways, such as impaired glucose metabolism or defective lipid metabolism, is associated with metabolic disorders like diabetes, obesity, and dyslipidemia. Alterations in organelle communication can also lead to pathological conditions. Mitochondrial dysfunction, characterized by impaired oxidative phosphorylation and increased production of reactive oxygen species, is implicated in various diseases, including neurodegenerative disorders and metabolic syndrome. Disrupted ER-mitochondria communication and impaired ER homeostasis contribute to the pathogenesis of diseases such as non-alcoholic fatty liver disease and neurodegenerative disorders. Furthermore, defects in lysosomal function and impaired organelle communication are associated with lysosomal storage disorders, neurodegenerative diseases, and age-related disorders. Disruptions in organelle communication can lead to the accumulation of toxic substances, impaired cellular clearance mechanisms, and cellular dysfunction.
Metabolic coordination and organelle communication are fundamental processes that underlie cellular metabolism and maintain cellular homeostasis. The interconnected metabolic pathways and the communication between organelles ensure efficient energy production, nutrient utilization, and cellular responses to changing conditions. Dysregulation of these processes can contribute to various diseases, highlighting the importance of understanding the mechanisms involved. Further research into the intricate interplay between metabolic coordination and organelle communication is necessary to unravel the complexities of cellular metabolism and its implications in health and disease. Targeting these processes may offer potential therapeutic avenues for the treatment of metabolic disorders, neurodegenerative diseases, and other related conditions. By unraveling the cellular perspective of metabolic coordination and organelle communication, we can gain valuable insights into cellular physiology and develop strategies to promote optimal cellular function and human health.
- Yan L, Qi Y, Huang X, et al.Structural basis for GTP hydrolysis and conformational change of MFN1 in mediating membrane fusion.Nat Struct Mol Biol. 2018;25(3):233-43.
- Franco A, Kitsis RN, Fleischer JA, et al.Correcting mitochondrial fusion by manipulating mitofusin conformations.Nature. 2016;540(7631):74-9.
- Liu J, Noel JK, Low HH.Structural basis for membrane tethering by a bacterial dynamin-like pair.Nat Commun. 2018;9(1):3345.
- Cerqua C, Anesti V, Pyakurel A, et al.Trichoplein/mitostatin regulates endoplasmic reticulum–mitochondria juxtaposition.EMBO Rep. 2010;11(11):854-60.
- Tian Y, Li B, Shi WZ, et al.Dynamin-related protein 1 inhibitors protect against ischemic toxicity through attenuating mitochondrial Ca2+ uptake from endoplasmic reticulum store in PC12 cells.Int J Mol Sci. 2014;15(2):3172-85.