Cristobal-Sarramian A, Radulovic M, Kohlwein S D
Institute of Molecular Biosciences, University of Graz and BioTechMed-Graz, Graz, Austria.
Institute of Molecular Biosciences, University of Graz and BioTechMed-Graz, Graz, Austria.
Methods Enzymol. 2017;588:395-412. doi: 10.1016/bs.mie.2016.09.087. Epub 2016 Nov 17.
Maintenance of cellular and organismal lipid homeostasis is critical for life, and any deviation from a balanced equilibrium between fat uptake and degradation may have deleterious consequences, resulting in severe lipid-associated disorders. Excess fat is typically stored in cytoplasmic organelles termed "lipid droplets" (LDs); to adjust for a constantly fluctuating supply of and demand for cellular fat, these organelles are metabolically highly dynamic and subject to multiple levels of regulation. In addition to a well-described cytosolic lipid degradation pathway, recent evidence underscores the importance of "lipophagy" in cellular lipid homeostasis, i.e., the degradation of LD by autophagy in the lysosome/vacuole. Pioneering work in yeast mutant models has unveiled the requirement of key components of the autophagy machinery, providing evidence for a highly conserved process of lipophagy from yeast to man. However, further work is required to unveil the intricate metabolic interaction between LD metabolism and autophagy to sustain membrane homeostasis and cellular survival.
维持细胞和机体的脂质稳态对生命至关重要,脂肪摄取与降解之间平衡的任何偏离都可能产生有害后果,导致严重的脂质相关疾病。多余的脂肪通常储存在称为“脂滴”(LDs)的细胞质细胞器中;为了适应细胞脂肪供应和需求的不断波动,这些细胞器在代谢上高度动态,并受到多种水平的调控。除了已被充分描述的胞质脂质降解途径外,最近的证据强调了“脂质自噬”在细胞脂质稳态中的重要性,即溶酶体/液泡中自噬对脂滴的降解。酵母突变体模型的开创性工作揭示了自噬机制关键成分的必要性,为从酵母到人高度保守的脂质自噬过程提供了证据。然而,还需要进一步的研究来揭示脂滴代谢与自噬之间复杂的代谢相互作用,以维持膜稳态和细胞存活。