Dataset Information

Metabolic alterations caused by the mutation and overexpression of the Tmem135 gene.

ABSTRACT:

Impact statement

Mitochondria are dynamic organelles undergoing fission and fusion. Proper regulation of this process is important for healthy aging process, as aberrant mitochondrial dynamics are associated with several age-related diseases/pathologies. However, it is not well understood how imbalanced mitochondrial dynamics may lead to those diseases and pathologies. Here, we aimed to determine metabolic alterations in tissues and cells from mouse models with over-fused (fusion > fission) and over-fragmented (fusion < fission) mitochondria that display age-related disease pathologies. Our results indicated tissue-dependent sensitivity to these mitochondrial changes, and metabolic pathways likely affected by aberrant mitochondrial dynamics. This study provides new insights into how dysregulated mitochondrial dynamics could lead to functional abnormalities of tissues and cells.

SUBMITTER: Lee WH

PROVIDER: S-EPMC7787545 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Metabolic alterations caused by the mutation and overexpression of the <i>Tmem135</i> gene.

Lee Wei-Hua WH Bhute Vijesh J VJ Higuchi Hitoshi H Ikeda Sakae S Palecek Sean P SP Ikeda Akihiro A

Experimental biology and medicine (Maywood, N.J.) 20200609 17

<h4>Impact statement</h4>Mitochondria are dynamic organelles undergoing fission and fusion. Proper regulation of this process is important for healthy aging process, as aberrant mitochondrial dynamics are associated with several age-related diseases/pathologies. However, it is not well understood how imbalanced mitochondrial dynamics may lead to those diseases and pathologies. Here, we aimed to determine metabolic alterations in tissues and cells from mouse models with over-fused (fusion > fissi ...[more]

PMID: 32515224

Similar Datasets

Project description:Mitochondria are highly dynamic organelles undergoing fusion, fission and degradation. Although mitochondria are known to be essential for cellular metabolism, it is not fully understood how mitochondrial dynamics affect cellular metabolism. We previously identified a mouse gene, transmembrane protein 135 (TMEM135) that plays a role in the regulation of mitochondrial dynamics. Mice with mutant Tmem135 (Tmem135FUN025/FUN025) show accelerated aging phenotypes and age-related pathologies in the retina including the retinal pigment epithelium (RPE). We also generated a transgenic mouse line globally overexpressing the Tmem135 gene (Tmem135 TG). In several tissues and cells that we studied such as the retina, heart and fibroblast cells, we observed that the Tmem135 mutation causes elongated mitochondria, while over-expression of Tmem135 results in fragmented mitochondria. These unique mouse models allow us to test how abnormal mitochondrial dynamics affect metabolic signatures of tissues and cells. In this study, we identified metabolic changes in primary RPE cell cultures as well as tissues isolated from Tmem135FUN025/FUN025 mice (fusion > fission) and Tmem135 TG mice (fusion < fission) using nuclear magnetic resonance (NMR) spectroscopy. Metabolomics analysis revealed a tissue-dependent response to alterations to Tmem135 whereby, significant metabolic changes were observed in heart in both mutant and TG mice as compared to WT while negligible effects were observed in cerebellum and hippocampus. We also observed changes in Tmem135FUN025/FUN025 and Tmem135 TG RPE cells associated with osmosis, glucose metabolism and phospholipid metabolism. Significant depletion of NAD+ was detected in both Tmem135FUN025/FUN025 and Tmem135 TG RPE cells, indicating that imbalance in mitochondrial dynamics to both directions lowers the cellular NAD+ level. Thus, we have identified metabolomic changes associated with imbalanced mitochondrial dynamics in heart tissue and RPE cells which can likely lead to functional abnormalities.