Degradation and beyond: the macrophage lysosome as a nexus for nutrient sensing and processing in atherosclerosis.
Degradation and beyond: the macrophage lysosome as a nexus for nutrient sensing and processing in atherosclerosis.
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DOI：
10.1097/mol.0000000000000213
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发表时间：
2015-10
影响因子：
4.4
通讯作者：
Razani B
中科院分区：
文献类型：
--
作者：
Sergin I;Evans TD;Razani B
The ability of macrophage lysosomes to degrade both exogenous and internally derived cargo is paramount to handling the overabundance of lipid and cytotoxic material present in the atherosclerotic plaque. We will discuss recent insights in both classical and novel functions of the lysosomal apparatus as it pertains to the pathophysiology of atherosclerosis. Lipid-mediated dysfunction in macrophage lysosomes appears to be a critical event in plaque progression. Consequences include enhanced inflammatory signaling (particularly the inflammasome/IL-1β axis) and an inability to interface with autophagy leading to a proatherogenic accumulation of dysfunctional organelles and protein aggregates. Aside from degradation, several novel functions have recently been ascribed to lysosomes including involvement in macrophage polarization, generation of lipid signaling intermediates, and serving as a nutrient depot for mTOR activation, each of which can have profound implications in atherosclerosis. Finally, the discovery of the transcription factor TFEB as a mechanism of inducing lysosomal biogenesis can have therapeutic value by reversing lysosomal dysfunction in macrophages. Lysosomes are a central organelle in the processing of exogenous and intracellular biomolecules. Together with recent data that implicates the degradation products of lysosomes in modulation of signaling pathways, these organelles truly do lay at a nexus in nutrient sensing and processing. Dissecting the full repertoire of lysosome function and ensuing dysfunction in plaque macrophages is pivotal to our understanding of atherogenesis.
