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| Status |
Public on Aug 01, 2024 |
| Title |
Developmental mitochondrial complex I activity determines lifespan |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Aberrant mitochondrial function has been associated with an increasingly large number of human disease states. Observations from in vivo models where mitochondrial function is altered suggest that adaptations to mitochondrial dysfunction may underpin disease pathology. We hypothesized that the severity of these maladaptations could be shaped by the plasticity of the system when mitochondrial dysfunction manifests. To investigate this, we have used inducible fly models of mitochondrial complex I (CI) dysfunction to reduce mitochondrial function at two stages of the fly lifecycle, from early development and adult eclosion. Here, we show that in early life (developmental) mitochondrial dysfunction results in severe reductions in survival and stress resistance in adulthood, while flies where mitochondrial function is perturbed from adulthood, are long-lived and stress resistant despite having up to an 75% reduction in CI activity. After excluding developmental defects as a cause, we went on to molecularly characterize these two populations of mitochondrially compromised flies, short- and long-lived. We find that our short-lived flies have unique transcriptomic and metabolomic responses which overlap significantly in discreet models of CI dysfunction. Our data demonstrate that early mitochondrial dysfunction via CI depletion elicits an adaptive response which severely reduces survival, while CI depletion from adulthood is not sufficient to reduce survival and stress resistance.
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| Overall design |
RNA-seq was performed on 3-5 day old whole Drosophila melanogaster males with depleted Complex I, achieved through RNAi targeting specific subunits and controls.
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| Contributor(s) |
Sanz A, Stefanatos R |
| Citation missing |
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| |
| Submission date |
Jul 10, 2023 |
| Last update date |
Aug 01, 2024 |
| Contact name |
Alberto Sanz |
| E-mail(s) |
alberto.sanzmontero@glasgow.ac.uk
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| Phone |
07864219015
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| Organization name |
University of Glasgow
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| Department |
School of Molecular Biosciences
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| Lab |
Sanz lab
|
| Street address |
Davidson Building
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| City |
Glasgow |
| ZIP/Postal code |
G12 8QQ |
| Country |
United Kingdom |
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| Platforms (2) |
| GPL22106 |
NextSeq 550 (Drosophila melanogaster) |
| GPL30203 |
NextSeq 2000 (Drosophila melanogaster) |
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| Samples (32)
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| Relations |
| BioProject |
PRJNA993400 |
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