Cited by 98Mitochondrial Function and PathologyPancreatic function and diabetesMetabolism, Diabetes, and Cancer

Diabetes-associated mitochondrial DNA mutation A3243G impairs cellular metabolic pathways necessary for beta cell function

Open access
de Andrade, P. B. M., Rubi, B., Frigerio, F., van den Ouweland, J. M. W., Maassen, J. A., Maechler, P.·2006·Diabetologia

Abstract

Aims/hypothesis Mitochondrial DNA (mtDNA) mutations cause several diseases, including mitochondrial inherited diabetes and deafness (MIDD), typically associated with the mtDNA A3243G point mutation on tRNALeu gene. The common hypothesis to explain the link between the genotype and the phenotype is that the mutation might impair mitochondrial metabolism expressly required for beta cell functions. However, this assumption has not yet been tested.Methods We used clonal osteosarcoma cytosolic hybrid cells (namely cybrids) harbouring mitochondria derived from MIDD patients and containing either exclusively wild-type or mutated (A3243G) mtDNA. According to the importance of mitochondrial metabolism in beta cells, we studied the impact of the mutation on key parameters by comparing stimulation of these cybrids by the main insulin secretagogue glucose and the mitochondrial substrate pyruvate.Results Compared with control mtDNA from the same patient, the A3243G mutation markedly modified metabolic pathways leading to a high glycolytic rate (2.8-fold increase), increased lactate production (2.5-fold), and reduced glucose oxidation (-83%). We also observed impaired NADH responses (-56%), negligible mitochondrial membrane potential, and reduced, only transient ATP generation. Moreover, cybrid cells carrying patient-derived mutant mtDNA exhibited deranged cell calcium handling with increased cytosolic loads (1.4-fold higher), and elevated reactive oxygen species (2.6-fold increase) under glucose deprivation.Conclusions/interpretation The present study demonstrates that the mtDNA A3243G mutation impairs crucial metabolic events required for proper cell functions, such as coupling of glucose recognition to insulin secretion.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s00125-006-0301-9

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Clonal cytosolic hybrid cells harboring mitochondria derived from MIDD patients exhibit impaired calcium handling and elevated ROS under metabolic stress.

    “Consistent with this view, clonal cytosolic hybrid cells harboring mitochondria derived from MIDD patients exhibit impaired calcium handling and elevated ROS under metabolic stress (247, 248).”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
de Andrade, P. B. M., Rubi, B., Frigerio, F., van den Ouweland, J. M. W., Maassen, J. A., & Maechler, P.
Affiliations
  • University of Geneva (CH)
  • Leiden University Medical Center (NL)
Corresponding author
Maechler, P.
Venue
Diabetologia
Published
2006-05-31
Volume
49
Issue
8
Pages
1816-1826
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
OpenAlex
W1979754659
Cited by
98
References
44
Citations by year
2025: 5 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 7 · 2018: 4 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 5
FWCI
3.54
Type
journal article
Language
en
Open access
Locations
  • Diabetologia (publishedVersion)
  • PubMed (publishedVersion)
  • reroDoc Digital Library (submittedVersion)
Funders
  • National Science Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • Fondation Leenaards
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
mitochondrial DNA A3243G mutation, mitochondrial diabetes, beta-cell function, mitochondrial metabolism, cybrids, glycolysis, glucose oxidation, lactic acid production, mitochondrial membrane potential, ATP production, calcium handling, reactive oxygen species, insulin secretion
MeSH terms
Insulin Secretion, Adenosine Triphosphate, Cell Line, Diabetes Mellitus, DNA, Mitochondrial, Glucose, Glycolysis, Humans, Insulin, Islets of Langerhans, Mutation, Polymorphism, Single Nucleotide

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review