Journal of Energy Bioscience 2025, Vol.16, No.1, 21-30 http://bioscipublisher.com/index.php/jeb 26 5.3 Cellular response to fluctuations in ATP demand Cells will make corresponding adjustments according to changes in ATP demand. The respiratory chain and oxidative phosphorylation systems of mitochondria play a central role, and the structure and activity of these systems can be regulated to adapt to different needs (Vercellino and Sazanov, 2021). For example, the heart can quickly switch between different energy sources to adapt to various situations (Karwi et al., 2019). PGC1 family proteins are important in regulating mitochondrial number and function, and they can also regulate metabolic processes, which is very helpful for cells (Coppi et al., 2021). The mitochondrial permeability transition pore (mPTP) also plays a role in regulating certain parts of the ATP synthase, especially in developmental or degeneration-related states (Mnatsakanyan and Jonas, 2020). 6 ATP and Cellular Stress Response 6.1 The role of ATP in apoptosis and survival pathways ATP is very important to cells. It not only provides energy, but also affects whether cells continue to live or enter the process of death. Mitochondria are the main source of ATP and play a key role in this process. When the permeability of the mitochondrial membrane increases, cell death may occur, which is an important step in the cell "suicide" process (intrinsic apoptosis). Mitochondria can also coordinate some cellular stress responses, such as autophagy (cells "eat" part of themselves) and necrosis, which help cells survive under stress (Galluzzi et al., 2012). In addition, protein kinase A (PKA) phosphorylates some subunits of cytochrome oxidase (COX), such as COXIV-1, which can regulate the energy flow of mitochondria, avoid ATP inhibition of COX, and help cells maintain normal function (Acín-Pérez et al., 2011). 6.2 Adaptation of ATP synthesis under hypoxic or nutrient-deficient conditions When cells are deprived of oxygen or nutrients, they will try to adjust their energy production methods so that ATP can continue to be synthesized. At this time, HIF-1α (a hypoxia-inducible factor) comes into play. It allows cells to increase glycolysis-related enzymes so that cells can use more glycolysis to replenish energy and make up for the lack of mitochondrial respiration (Kierans and Taylor, 2020). There is also a protein kinase called AMPK, which is also activated when energy is insufficient. AMPK can increase ATP production and reduce energy waste by phosphorylating some enzymes or growth control points (Herzig and Shaw, 2017). Hypoxia signals and the AMPK/mTOR signaling pathway also interact with each other, which allows cells to better adapt to hypoxia and try to ensure that ATP can continue to be produced (Chun and Kim, 2021). 6.3 Mitochondrial adaptation to maintain ATP homeostasis In order to cope with changes in energy demand, mitochondria will also make some adjustments to try to maintain a stable supply of ATP. Mitochondria change shape, sometimes merge together, sometimes separate, and move inside the cell to where energy is more needed, so that energy can be distributed more rationally (Yu and Pekkurnaz, 2018). The respiratory chain of mitochondria needs to be properly assembled and regulated so that electron transfer is efficient and ATP can be synthesized efficiently. The formation of respiratory supercomplexes can improve this efficiency (Vercellino and Sazanov, 2021). When mitochondria are stressed, they also initiate some protective mechanisms, such as mitophagy (removal of damaged mitochondria) and UPR^MT (a mechanism for processing unfolded proteins), which help maintain the quality and function of mitochondria and ensure that ATP continues to be produced steadily (Hill and Remmen, 2014). 7 Pathologies Associated with ATP Dysregulation 7.1 Disorders of ATP production (e.g., mitochondrial diseases) Mitochondrial diseases are usually caused by problems with ATP production. Most of these diseases are caused by defects in the mitochondrial respiratory chain, which is important for the production of ATP through oxidative phosphorylation. The mitochondrial oxidative phosphorylation system consists of five enzyme complexes and two electron carriers that work together to produce ATP. If this system goes wrong, different types of mitochondrial diseases may result, which also shows that we need to understand how these complexes are assembled and regulated (Vercellino and Sazanov, 2021). If the mitochondrial ATP synthase is damaged under pathological
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