The metabolic balance between catabolism in the mitochondria and anabolism in the endoplasmic reticulum (ER) is essential for maintaining cellular homeostasis. For example, the proteins synthesized by the ER are transported to the mitochondria, where they are broken down into their component molecules, and the lipids and some proteins synthesized by the mitochondria are transported to the ER, where they are stored and used in the anabolic process. The mutual relationship between these two organelles is essential for the production of energy and the synthesis of important molecules such as proteins, lipids, carbohydrates, and hormones.
Despite their finely tuned interactions, both organelles orchestrate inter-organelle communication with other intracellular organelles through their physical contact sites, signal transduction pathways, and vesicle transport mechanisms. These surrounding intracellular organelles include the nucleus, Golgi apparatus, lipid droplets, peroxisomes, and lysosomes. These inter-organelle interactions promote cell survival and growth through ongoing challenges.
The AMP-activated protein kinase (AMPK) and Target-of-rapamycin (TOR) signaling pathways modulate nutrient sensing and regulation through cellular metabolic adaptation. AMPK, the Yin or "dark side," is activated during the low availability of energy or nutrient and promotes autophagy to continue energy generation and recycle biomolecules for new proteins and membranes. This adaptation maintains cell viability while inhibiting cell growth. On the other hand, the Yang or "bright side," the TOR pathway is activated with high nutrient availability and promotes anabolic growth and proliferation. These opposing pathways work together to help cells adjust cellular metabolism according to the available resources, thus allowing cells to respond to environmental changes. These responses also involve calcium homeostasis, redox balance, proteostasis, autophagic degradation, and apoptotic cell death. These integrated stress responses help to restore homeostasis and ensure that the cell can produce the energy and molecules it needs for survival.
To summarize, the balance between catabolism, or Yin, in mitochondria and anabolism, or Yang, in the ER is crucial for maintaining cellular homeostasis. Both metabolisms are interdependent and one cannot function without the other. Their integrated functions maintain cellular homeostasis and are adapted to host nutrient availability through AMPK and TOR pathways.
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