| 英文摘要 |
In 2014, more than 26 review articles related to antiaging, anti-inflammatory and antioxidative effects of herbal drugs appeared. Free radicals or reactive oxygen species (ROS) are majorly produced by mitochondria (Mt) and malfunction of Mt has been hypothesized as the fundamental factor causing the chronic inflammation and aging. Mt is an endomicrobiota, rickettsia like α-purple bacteria, an anerobe which engulfed the bacteria that using oxygen and sugar to keep the energy in ATP. The proteins encoded by nuclear and Mt DNA affected each other’s functions. Mt is well interacted with endoplasmic reticulum (ER) on mitochondriaassociated ER membranes (MAMs). Mt process redoxidation, biogenesis, degradation, fission, fusion, and transport along the cell extremity continuously. The fusion mixed the metabolites, proteins, and mtDNA, while fission segregated the damaged component of Mt and rearranged Mt by mitophagy, the selective degradation of mitochondria by autophagy. Calcium (Ca2+) is transported from ER to Mt through permeability transition pore by Mt Ca2+ uniporter, and transmembrane inositol 1, 4, 5-triphosphate receptor (IP3R). IP3R interacted with mTORC2 at MAM to regulate voltage-dependent anion channel (VDAC) on outer Mt membrane through glucose-regulated protein 75, to perform the exchange of metabolites and ions, and also involved in the inhibition of ER stress and apoptosis. while, mTORC1 controls mitophagy, mitochondrial activity and biogenesis. The cytochrome C released from Mt blocked the Ca2+-induced IP3R inhibition, and then increased Ca2+ release from ER and cytochrome C from Mt. VDAC interacted with hexokinase 2 (HK2) and B-cell lymphocytic protein-2 (Bcl2) decreased the entrance of Ca2+ from ER to Mt, then decreased ROS production. Promyelocytic leukemia nuclear bodies form a complex with IP3R, which is involved in Ca2+ and apoptosis regulation. Phophatase and tensin homolog deleted on chromosome 10 (PTEN) antagonized Akt-induced IP3R inhibition and Ca2+ release from ER. PTEN-induced putative kinase 1 (PINK1) recruits parkin, then selectively degrades the microtube-associated protein light chain 3 alpha. Mitophagy is the process to deplete damaged Mt by lysosome which control the function of MAMs, Ca2+ uptake, bioenergetics of Mt, and apoptosis through IP3R, HK2 and phosphofurin acidic cluster sorting protein 2. NLRP3 inflammasomes located in ER are activated and migrated to MAMs by ROS. Stimulator of interferon genes with retinoic acid-induced gene-like helicase stabilized the MAMs, but activated type I interferon production. The activity of pyruvate dehydrogenase phosphatase is related to carcinogenesis. The point mutation of mtDNA promotes cancer metastases and drug resistance to some anticancer agents. The ATP binding cassette (ABC) is located in inner Mt and nucleotide binding domain. ABC regulates the communication between nuclear and cytosol. The mutation of ABC protein B7, a cytosolic-nuclear iron-sulfur protein, caused the sideroblastic anemia and cerebellar ataxia. The targets methods, and rational for the development of antiaging, anti-oxidant, or anti-inflammatory drugs are mentioned in the text. |
