Dataset Information

NMR metabolomics of fibroblasts with inherited mitochondrial Complex I mutation reveals treatment-reversible lipid and amino acid metabolism alterations.

ABSTRACT:

Introduction

Elucidating molecular alterations due to mitochondrial Complex I (CI) mutations may help to understand CI deficiency (CID), not only in mitochondriopathies but also as it is caused by drugs or associated to many diseases.

Objectives

CID metabolic expression was investigated in Leber's hereditary optic neuropathy (LHON) caused by an inherited mutation of CI.

Methods

NMR-based metabolomics analysis was performed in intact skin fibroblasts from LHON patients. It used several datasets: one-dimensional ¹H-NMR spectra, two-dimensional ¹H-NMR spectra and quantified metabolites. Spectra were analysed using orthogonal partial least squares-discriminant analysis (OPLS-DA), and quantified metabolites using univariate statistics. The response to idebenone (IDE) and resveratrol (RSV), two agents improving CI activity and mitochondrial functions was evaluated.

Results

LHON fibroblasts had decreased CI activity (-?43%, p??1 in OPLS-DA, p??1) and alanine (VIP?>?1, p??1 and/or p?ConclusionLHON fibroblasts display lipid and amino acid metabolism alterations that are reversed by mitochondria-targeted treatments, and can be related to adaptive changes. Findings bring insights into molecular changes induced by CI mutation and, beyond, CID of other origins.

SUBMITTER: Morvan D

PROVIDER: S-EPMC5968059 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

NMR metabolomics of fibroblasts with inherited mitochondrial Complex I mutation reveals treatment-reversible lipid and amino acid metabolism alterations.

Morvan Daniel D Demidem Aicha A

Metabolomics : Official journal of the Metabolomic Society 20180322 5

<h4>Introduction</h4>Elucidating molecular alterations due to mitochondrial Complex I (CI) mutations may help to understand CI deficiency (CID), not only in mitochondriopathies but also as it is caused by drugs or associated to many diseases.<h4>Objectives</h4>CID metabolic expression was investigated in Leber's hereditary optic neuropathy (LHON) caused by an inherited mutation of CI.<h4>Methods</h4>NMR-based metabolomics analysis was performed in intact skin fibroblasts from LHON patients. It u ...[more]

PMID: 29937703

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Dataset Information

NMR metabolomics of fibroblasts with inherited mitochondrial Complex I mutation reveals treatment-reversible lipid and amino acid metabolism alterations.

Introduction

Objectives

Methods

Results

Publications

NMR metabolomics of fibroblasts with inherited mitochondrial Complex I mutation reveals treatment-reversible lipid and amino acid metabolism alterations.

Similar Datasets

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