Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
J Pathol. 2012 Jan;226(2):255-73. doi: 10.1002/path.3025. Epub 2011 Nov 23.
Autophagy is a process traditionally known to contribute to cellular cleaning through the removal of intracellular components in lysosomes. In recent years, intensive scrutiny at the molecular level to which autophagy has been subjected has also contributed to expanding our understanding of the physiological role of this pathway. Added to the well-characterized role in quality control, autophagy has proved to be important in the maintenance of cellular homeostasis and of the energetic balance, in cellular and tissue remodelling, and cellular defence against extracellular insults and pathogens. It is not a surprise that, in light of this growing number of physiological functions, connections between autophagic malfunction and human pathologies have also been strengthened. In this review, we focus on several pathological conditions associated with primary or secondary defects in autophagy and comment on a recurring theme for many of them, ie the fact that autophagy can often exert both beneficial and aggravating effects on the progression of disease. Elucidating the factors that determine the switch between these dual functions of autophagy in disease has become a priority when considering the potential therapeutic implications of the pharmacological modulation of autophagy in many of these pathological conditions.
自噬是一个传统上被认为通过溶酶体清除细胞内成分来促进细胞清洁的过程。近年来，对自噬分子水平的深入研究也有助于扩大我们对这条途径的生理作用的理解。除了在质量控制方面的作用外，自噬在维持细胞内环境平衡和能量平衡、细胞和组织重塑以及细胞对细胞外刺激和病原体的防御方面也被证明是重要的。鉴于自噬的这些不断增加的生理功能，自噬功能障碍与人类疾病之间的联系也得到了加强，这并不奇怪。在这篇综述中，我们关注了几种与自噬原发性或继发性缺陷相关的病理状况，并对其中许多病理状况的一个反复出现的主题进行了评论，即自噬通常对疾病的进展既有有益的影响也有加重的影响。在考虑在许多这些病理状况下通过药物调节自噬的潜在治疗意义时，阐明决定自噬在疾病中这两种功能之间转换的因素已成为当务之急。
