Journal of Energy Bioscience 2025, Vol.16, No.1, 42-52 http://bioscipublisher.com/index.php/jeb 44 brain because these places have a particularly high demand for energy (Kazak and Cohen, 2020; Bonilla et al., 2021a). When the body needs energy, CK will react in the opposite direction, breaking down PCr and releasing ATP at the same time. This ATP is then used for various cellular activities. Figure 1 General overview of the CK/PCr system (Adopted from Bonilla et al., 2021a) Image caption: This diagram illustrates the integrated subcellular network of energy production and mechanical processes in creatine (Cr) metabolism, highlighting the chemo-mechanical energy transduction system. Key components include the mitochondrial reticulum (involving oxidative metabolism and the mitochondrial interactosome), the phosphagen and glycolytic systems for ATP production, the linker of nucleoskeleton and cytoskeleton (LINC) complex interacting with nesprins, microtubules, actin polymerization, and β-tubulin, as well as motor proteins and ion pumps like SERCA and Na+/K+-ATPase for Ca2+ regulation. Green sparkles mark areas where the creatine kinase/phosphocreatine (CK/PCr) system is essential for functionality. To simplify visualization, detailed structures such as ER-mitochondria networks, TIM/TOM complexes, and cytoskeletal architecture are omitted. This representation underscores the interdependence of these systems in maintaining cellular energy and mechanical functions. CK: Creatine kinase; PCr: Phosphocreatine; SERCA: Sarco/Endoplasmic Reticulum Ca2+ ATPase; TIM/TOM: Translocases of the inner/outer mitochondrial membranes; VDAC: Voltage-dependent anion channel Source: designed by the authors (D.A.B.) using figure templates developed by Servier Medical Art (Les Laboratoires Servier, Suresnes, France), licensed under a Creative Common Attribution 3.0 Generic License. http://smart.servier.com/ (accessed on 14 January 2021) (Adapted from Bonilla et al., 2021a) 3.2 Role of mitochondria and cytosolic enzymes in creatine phosphate pathways The enzymes in mitochondria and cytoplasm also play a key role in the phosphocreatine system. Creatine kinase (MtCK) in mitochondria is located in the gap of the mitochondrial membrane. It uses ATP produced by mitochondria to synthesize PCr. The synthesized PCr can diffuse into the cytoplasm, and then CK in the cytoplasm uses it to synthesize ATP from ADP. This method is like an energy transfer station, which can quickly provide ATP buffer (Kazak and Spiegelman, 2020; Wallimann et al., 2020). This "shuttle system" ensures that the ATP produced by mitochondria can be effectively delivered to where the cell needs energy (Franco et al., 2021; Sun et al., 2021). In addition, mitochondria can form a network, so that energy can be transmitted farther without too much diffusion of metabolites, making the entire PCr system work more efficiently (Kazak and Cohen, 2020; Franco et al., 2021).
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