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A Metabolic Signature of Mitochondrial Dysfunction Revealed through a Monogenic Form of Leigh Syndrome.

Thompson Legault J, Strittmatter L, Tardif J, Sharma R, Tremblay-Vaillancourt V, Aubut C, Boucher G, Clish CB, Cyr D, Daneault C, Waters PJ, LSFC ConsortiumVachon L, Morin C, Laprise C, Rioux JD, Mootha VK, Des Rosiers C - Cell Rep (2015)

Bottom Line: A decline in mitochondrial respiration represents the root cause of a large number of inborn errors of metabolism.It is also associated with common age-associated diseases and the aging process.Our study identifies systemic, metabolic pathway derangements that can lie downstream of primary mitochondrial lesions, with implications for understanding how the organelle contributes to rare and common diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutrition, Université de Montréal, Montreal, QC H3C 3J7, Canada; Research Centre, Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.

No MeSH data available.


Related in: MedlinePlus

Individual Analytes with Statistical Significance in LSFC Patients versus Controls(A) Platform 1; (B) Platform 2. Each dot represents a log2-transformed patient/matched control ratio. Metabolites are ordered by mean log2-transformed patient/control ratio. See also Figure S2 for data presented as volcano plots, Figure S1 for a summary of measured analytes, and Table S2 for log2-transformed ratios and p values of all analytes.
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Figure 2: Individual Analytes with Statistical Significance in LSFC Patients versus Controls(A) Platform 1; (B) Platform 2. Each dot represents a log2-transformed patient/matched control ratio. Metabolites are ordered by mean log2-transformed patient/control ratio. See also Figure S2 for data presented as volcano plots, Figure S1 for a summary of measured analytes, and Table S2 for log2-transformed ratios and p values of all analytes.

Mentions: The two data sets were then independently subjected to permutation analyses, and statistical significance was reached between patients and controls for 24 analytes/ratios out of 137 in Platform 1 (p < 0.03) and for 31 analytes out of 156 in Platform 2 (p < 0.023), with an overlap of nine significant metabolites between both platforms (Table S4). All analytes are depicted as volcano plots in Figure S2 and listed in Table S2. Combining the results of both platforms, 46 single variables (representing 45 unique compounds/ratios) out of the 256 single variables submitted to the permutation test were statistically different between LSFC patients and controls, as depicted in Figure 2. Of note, the compound heterozygote was similar to the other LSFC patients (A354V homozygotes).


A Metabolic Signature of Mitochondrial Dysfunction Revealed through a Monogenic Form of Leigh Syndrome.

Thompson Legault J, Strittmatter L, Tardif J, Sharma R, Tremblay-Vaillancourt V, Aubut C, Boucher G, Clish CB, Cyr D, Daneault C, Waters PJ, LSFC ConsortiumVachon L, Morin C, Laprise C, Rioux JD, Mootha VK, Des Rosiers C - Cell Rep (2015)

Individual Analytes with Statistical Significance in LSFC Patients versus Controls(A) Platform 1; (B) Platform 2. Each dot represents a log2-transformed patient/matched control ratio. Metabolites are ordered by mean log2-transformed patient/control ratio. See also Figure S2 for data presented as volcano plots, Figure S1 for a summary of measured analytes, and Table S2 for log2-transformed ratios and p values of all analytes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644511&req=5

Figure 2: Individual Analytes with Statistical Significance in LSFC Patients versus Controls(A) Platform 1; (B) Platform 2. Each dot represents a log2-transformed patient/matched control ratio. Metabolites are ordered by mean log2-transformed patient/control ratio. See also Figure S2 for data presented as volcano plots, Figure S1 for a summary of measured analytes, and Table S2 for log2-transformed ratios and p values of all analytes.
Mentions: The two data sets were then independently subjected to permutation analyses, and statistical significance was reached between patients and controls for 24 analytes/ratios out of 137 in Platform 1 (p < 0.03) and for 31 analytes out of 156 in Platform 2 (p < 0.023), with an overlap of nine significant metabolites between both platforms (Table S4). All analytes are depicted as volcano plots in Figure S2 and listed in Table S2. Combining the results of both platforms, 46 single variables (representing 45 unique compounds/ratios) out of the 256 single variables submitted to the permutation test were statistically different between LSFC patients and controls, as depicted in Figure 2. Of note, the compound heterozygote was similar to the other LSFC patients (A354V homozygotes).

Bottom Line: A decline in mitochondrial respiration represents the root cause of a large number of inborn errors of metabolism.It is also associated with common age-associated diseases and the aging process.Our study identifies systemic, metabolic pathway derangements that can lie downstream of primary mitochondrial lesions, with implications for understanding how the organelle contributes to rare and common diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutrition, Université de Montréal, Montreal, QC H3C 3J7, Canada; Research Centre, Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.

No MeSH data available.


Related in: MedlinePlus