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酵母细胞暴露于外源性棕榈油酸,要么适应应激并存活,要么启动受调控的脂细胞坏死并死亡。

Yeast Cells Exposed to Exogenous Palmitoleic Acid Either Adapt to Stress and Survive or Commit to Regulated Liponecrosis and Die.

机构信息

Concordia University, Department of Biology, Montreal, QC, Canada H4B 1R6.

出版信息

Oxid Med Cell Longev. 2018 Jan 31;2018:3074769. doi: 10.1155/2018/3074769. eCollection 2018.

Abstract

A disturbed homeostasis of cellular lipids and the resulting lipotoxicity are considered to be key contributors to many human pathologies, including obesity, metabolic syndrome, type 2 diabetes, cardiovascular diseases, and cancer. The yeast has been successfully used for uncovering molecular mechanisms through which impaired lipid metabolism causes lipotoxicity and elicits different forms of regulated cell death. Here, we discuss mechanisms of the "liponecrotic" mode of regulated cell death in . This mode of regulated cell death can be initiated in response to a brief treatment of yeast with exogenous palmitoleic acid. Such treatment prompts the incorporation of exogenously added palmitoleic acid into phospholipids and neutral lipids. This orchestrates a global remodeling of lipid metabolism and transfer in the endoplasmic reticulum, mitochondria, lipid droplets, and the plasma membrane. Certain features of such remodeling play essential roles either in committing yeast to liponecrosis or in executing this mode of regulated cell death. We also outline four processes through which yeast cells actively resist liponecrosis by adapting to the cellular stress imposed by palmitoleic acid and maintaining viability. These prosurvival cellular processes are confined in the endoplasmic reticulum, lipid droplets, peroxisomes, autophagosomes, vacuoles, and the cytosol.

摘要

细胞脂质平衡失调和由此产生的脂毒性被认为是许多人类疾病的主要诱因,包括肥胖、代谢综合征、2 型糖尿病、心血管疾病和癌症。酵母已被成功用于揭示受损脂质代谢导致脂毒性并引发不同形式的细胞程序性死亡的分子机制。在这里,我们讨论酵母中“脂坏死”型细胞程序性死亡的机制。这种细胞程序性死亡的模式可以通过短暂地用外源性棕榈油酸处理酵母来启动。这种处理促使外源性添加的棕榈油酸掺入磷脂和中性脂质。这协调了内质网、线粒体、脂滴和质膜中脂质代谢和转移的全局重构。这种重构的某些特征在酵母细胞向脂坏死的转化或执行这种细胞程序性死亡的模式中起着至关重要的作用。我们还概述了酵母细胞通过适应棕榈油酸施加的细胞应激并保持活力来积极抵抗脂坏死的四个过程。这些细胞生存过程局限在内质网、脂滴、过氧化物酶体、自噬体、液泡和细胞质中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a72a/5831759/45baff3e5005/OMCL2018-3074769.001.jpg

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