线粒体自噬(mitophagy)是指特异清除受损或多余线粒体的过程,是一种重要的线粒体质量控制机制。线粒体自噬功能障碍或线粒体自噬过度激活都会破坏线粒体稳态,影响机体健康甚至导致死亡。主要讨论了在酵母和哺乳动物细胞中发现的正向调...线粒体自噬(mitophagy)是指特异清除受损或多余线粒体的过程,是一种重要的线粒体质量控制机制。线粒体自噬功能障碍或线粒体自噬过度激活都会破坏线粒体稳态,影响机体健康甚至导致死亡。主要讨论了在酵母和哺乳动物细胞中发现的正向调控线粒体自噬的机制:在酵母中,线粒体自噬是由自噬相关蛋白32(autophagy-related protein 32,Atg32)介导的;而哺乳动物体内线粒体自噬的调控途径主要有3种:PTEN诱导激酶1(PTEN-induced kinase 1,PINK1)/E3泛素连接酶Parkin途径、类NIP3蛋白X(NIP3-like protein X,Nix)途径、携带FUN14结构域蛋白1(FUN14 domain-containing protein 1,UNDC1)途径,此外,还有几种新发现的线粒体自噬受体也能够介导线粒体的特异清除。并对目前研究较少的线粒体自噬的负调控机制进行了综述。最后探讨了线粒体自噬功能异常与人类疾病(如帕金森症)的关联。通过深入剖析线粒体自噬发生的分子机制,以期为进一步研究与线粒体自噬功能异常相关的疾病的治疗提供理论基础。展开更多
Pneumonia, the most typical and frequent lower respiratory tract infection （LRTI）, is a leading cause of health problems in the United States. Bacteria represent the most prevailing cause of pneumonia in both childr...Pneumonia, the most typical and frequent lower respiratory tract infection （LRTI）, is a leading cause of health problems in the United States. Bacteria represent the most prevailing cause of pneumonia in both children and adults. Although pneumonia with a single bacterial infection is common, a significant portion of patients with pneumonia is polymicrobial. This infection is often complexed with other physiological factors such as cytokines and growth factors. Nontypeable Haemophilus influenzae （NTHi） is the most frequently recovered Gram-negative bacterial pathogen in the respiratory system and induces strong inflammatory responses. NTHi also synergizes with other respiratory pathogens, such as Streptococcus pneumoniae and respiratory viruses and pro-inflammatory cytokines, such as tumor necrosis factor-alpha （TNF-α）. It is noteworthy that NTHi not only synergizes with growth factors such as transforming growth factor-beta （TGF-β）, but also utilizes growth factor receptors such as TGF-β receptor and epidermal growth factor receptor （EGFR）, to enhance inflammatory responses. Although appropriate inflammation is a protective response against invading pathogens, an uncontrolled inflammatory response is often detrimental to the host. Thus, inflammation must be tightly regulated. The human immune system has evolved strategies for controlling overactive inflammatory response. One such important mechanism is via regulation of negative feedback regulators for inflammation. CYLD, a multifunctional deubiquitinase, was originally reported as a tumor suppressor, but was recently identified as a negative regulator for nuclear factor-kappa B （NF-κB） signaling. It is induced by NTHi and TNF-α via a NF-κB-dependent mechanism, thereby serving as an inducible negative feedback regulator for tightly controlling inflammation in NTHi infection.展开更多
文摘线粒体自噬(mitophagy)是指特异清除受损或多余线粒体的过程,是一种重要的线粒体质量控制机制。线粒体自噬功能障碍或线粒体自噬过度激活都会破坏线粒体稳态,影响机体健康甚至导致死亡。主要讨论了在酵母和哺乳动物细胞中发现的正向调控线粒体自噬的机制:在酵母中,线粒体自噬是由自噬相关蛋白32(autophagy-related protein 32,Atg32)介导的;而哺乳动物体内线粒体自噬的调控途径主要有3种:PTEN诱导激酶1(PTEN-induced kinase 1,PINK1)/E3泛素连接酶Parkin途径、类NIP3蛋白X(NIP3-like protein X,Nix)途径、携带FUN14结构域蛋白1(FUN14 domain-containing protein 1,UNDC1)途径,此外,还有几种新发现的线粒体自噬受体也能够介导线粒体的特异清除。并对目前研究较少的线粒体自噬的负调控机制进行了综述。最后探讨了线粒体自噬功能异常与人类疾病(如帕金森症)的关联。通过深入剖析线粒体自噬发生的分子机制,以期为进一步研究与线粒体自噬功能异常相关的疾病的治疗提供理论基础。
文摘Pneumonia, the most typical and frequent lower respiratory tract infection （LRTI）, is a leading cause of health problems in the United States. Bacteria represent the most prevailing cause of pneumonia in both children and adults. Although pneumonia with a single bacterial infection is common, a significant portion of patients with pneumonia is polymicrobial. This infection is often complexed with other physiological factors such as cytokines and growth factors. Nontypeable Haemophilus influenzae （NTHi） is the most frequently recovered Gram-negative bacterial pathogen in the respiratory system and induces strong inflammatory responses. NTHi also synergizes with other respiratory pathogens, such as Streptococcus pneumoniae and respiratory viruses and pro-inflammatory cytokines, such as tumor necrosis factor-alpha （TNF-α）. It is noteworthy that NTHi not only synergizes with growth factors such as transforming growth factor-beta （TGF-β）, but also utilizes growth factor receptors such as TGF-β receptor and epidermal growth factor receptor （EGFR）, to enhance inflammatory responses. Although appropriate inflammation is a protective response against invading pathogens, an uncontrolled inflammatory response is often detrimental to the host. Thus, inflammation must be tightly regulated. The human immune system has evolved strategies for controlling overactive inflammatory response. One such important mechanism is via regulation of negative feedback regulators for inflammation. CYLD, a multifunctional deubiquitinase, was originally reported as a tumor suppressor, but was recently identified as a negative regulator for nuclear factor-kappa B （NF-κB） signaling. It is induced by NTHi and TNF-α via a NF-κB-dependent mechanism, thereby serving as an inducible negative feedback regulator for tightly controlling inflammation in NTHi infection.
