Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA.
Semin Cell Dev Biol. 2010 Sep;21(7):712-8. doi: 10.1016/j.semcdb.2010.04.004. Epub 2010 Apr 18.
Autophagy is a key cytoplasmic biomass and organellar quality and quantity control pathway of the eukaryotic cell. It is particularly suited to capture and degrade large, multi-macromolecular cytosplasmic targets earmarked for degradation or turnover. Typical autophagic cargos represent large swaths of cytosol as a source of energy and anabolic precursors at times of growth restrictions imposed by the absence of growth factors, nutrient limitation or hypoxia. Autophagy is the only effective mechanism for removal of whole organelles such as leaky or surplus mitochondria, disposal of potentially toxic protein aggregates too large for proteasomal removal, and elimination of intracellular microbes including bacteria, protozoa and viruses. Recent studies have shown that human immunodeficiency virus (HIV) is targeted for eliminated by autophagy but that this is countered by the viral protein Nef. Here we review these relationships and underscore the untapped potential of autophagy as a druggable antiviral process.
自噬是真核细胞细胞质生物量和细胞器质量及数量的关键控制途径。它特别适合捕获和降解大型、多分子的细胞质靶标,这些靶标被指定用于降解或周转。典型的自噬 cargos 代表了大量的细胞质,作为在缺乏生长因子、营养限制或缺氧等生长受限情况下的能量和合成前体的来源。自噬是去除整个细胞器的唯一有效机制,如渗漏或多余的线粒体,清除太大而无法通过蛋白酶体去除的潜在毒性蛋白聚集体,以及消除包括细菌、原生动物和病毒在内的细胞内微生物。最近的研究表明,人类免疫缺陷病毒 (HIV) 是自噬的靶标,但病毒蛋白 Nef 会对此进行拮抗。在这里,我们回顾了这些关系,并强调了自噬作为一种可用药的抗病毒过程的未开发潜力。