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Expression data from Col-0 and mcu123 roots of 20-d-old seedlings grown in a sterile hydroponic system.

ABSTRACT: Ca2+ signaling is central to plant development, modulating gene expression to enable highly specific plant responses. While Ca2+-responsive proteins have been investigated intensely in plants, only few Ca2+ channels are known, and our understanding of how intracellular Ca2+ fluxes are facilitated remains limited. We obtained an Arabidopsis triple knockout mutant of homologues of the mammalian mitochondrial Ca2+ channel-forming MCU protein, in which mitochondrial Ca2+ uptake was severly perturbed in vivo in roots. To pinpoint the impact of the distrupted mitochondrial matrix free Ca2+ dynamcis, we performed transcriptome analysis in roots of an MCU triple knockout background (mcu123) and its corresponding wild type background (Col-0). We devised a microarray-based analysis to investigate transcriptome differences in roots of mcu123 triple knockout backgroudn and Col-0, without additional stimulation, and idenfitied distinct classes of differentially abundant transcripts.

ORGANISM(S): Arabidopsis thaliana

PROVIDER: GSE152581 | GEO | 2022/07/18

REPOSITORIES: GEO

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Project description:Chronic low-grade inflammation is a hallmark of aging, but its etiology is not well understood. Mitochondrial dysfunction has been linked to both cellular senescence and age-related inflammation or inflammaging but fundamental mechanisms underlying these links are unclear. We analyzed age-related gene expression in different human tissues and discovered that in blood, the mRNA expression of Mitochondrial Calcium Uniporter (MCU) and its regulatory subunit MICU1 correlated inversely with age. MCU is the pore-forming subunit of a Ca2+-selective ion channel complex residing in the mitochondrial inner membrane and is the main conduit for Ca2+-influx into the mitochondrial matrix. Based on these findings we tested the simple hypothesis that mitochondrial Ca2+ uptake capacity of macrophages decreases with age. We found a significant reduction in the mitochondrial Ca2+-uptake capacity of macrophages derived from aged (80-90 weeks) mice. Notably, these macrophages display amplified cytosolic Ca2+ elevations and increased inflammatory output. To test the salience of mitochondrial calcium uptake in regulating macrophage inflammatory output, we deleted Mcu selectively in macrophages. The Mcu-/- macrophages of young mice (<25 weeks) express more inflammatory genes at baseline and show a hyper-inflammatory response when stimulated. We show that reduced mitochondrial Ca2+ amplifies cytosolic Ca2+ oscillations and potentiates downstream NFkB activation, which is central to inflammation. The regulation of inflammatory response by mitochondrial Ca2+ uptake is also seen readily in human macrophages. The siRNA-mediated knockdown of MCU in human blood derived macrophages recapitulates the phenomenon – the mitochondrial Ca2+-uptake is greatly reduced, cytosolic Ca2+ elevations are more pronounced, and the macrophages are hyper-inflammatory. Our findings pinpoint the MCU complex as a keystone molecular apparatus that links age-related changes in mitochondrial physiology to macrophage-mediated inflammation. Resident macrophages are intrinsic to every organ system and the steady erosion of their mitochondrial Ca2+-uptake capacity may play a germinal or exacerbating role in many age-related neurodegenerative, cardiometabolic, renal and musculoskeletal diseases that afflict us.

Dataset Information

Expression data from Col-0 and mcu123 roots of 20-d-old seedlings grown in a sterile hydroponic system.

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