Mitochondrial biogenesis and human disease
Lead Research Organisation:
MRC Centre Cambridge
Abstract
Mitochondria have a central role in producing energy in a suitable form for biological processes. They are also involved in programmed cell death, and in maintaining appropriate levels of calcium in cells. These activities require mitochondria to communicate with the cellular nucleus, and one way that signalling is carried out involves very reactive oxygen molecules that are generated in mitochondrion. When these processes go wrong, they can lead to human diseases including heart disease, diabetes, neurodegenerative disorders, obesity and cancer. If we understand the basic processes, we are more likely to understand what is happening when these processes in the mitochondrion go wrong, and to be able to provide therapies to compensate for or correct the faults. This programme will study how the mitochondria themselves are made and put together, and how they increase their numbers in response to the changing requirements of the cell. It will try and to provide diagnostic tests and therapies for patients when these processes no longer work properly.|
Technical Summary
The biogenesis of mitochondria is a complex process controlled by communication between the nucleus and the organelle. It requires the coordination of the cytoplasmic synthesis and import into the organelle of about 1,500 proteins encoded in the nucleus, with the synthesis in the organelle of 13 proteins encoded by mtDNA, followed by the assembly of multisubunit enzyme complexes containing proteins from both genomes. In addition, it involves the regulation of fission and fusion of mitochondria, and of the turnover of mitochondria by mitophagy in response to various stimuli. Disruption of any of these processes in human can lead to defective mitochondria and pathology. The aim of this programme is to identify the mechanisms involved in biogenesis of mitochondria especially those involving the mitochondrial inner membrane protein, MPV17.
Organisations
- MRC Centre Cambridge, United Kingdom (Lead Research Organisation)
- University of Oxford, United Kingdom (Collaboration)
- University of Cambridge (Collaboration)
- Tsuyama Central Hospital (Collaboration)
- Newcastle University, United Kingdom (Collaboration)
- Vall d'Hebron University Hospital (Collaboration)
Publications

Dalla Rosa I
(2014)
MPV17L2 is required for ribosome assembly in mitochondria.
in Nucleic acids research

He J
(2012)
Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.
in Nucleic acids research

Johnson MA
(2014)
Amino acid starvation has opposite effects on mitochondrial and cytosolic protein synthesis.
in PloS one

Pearce S
(2013)
Mitochondrial diseases: translation matters.
in Molecular and cellular neurosciences

Spinazzola A
(2011)
Mitochondrial DNA mutations and depletion in pediatric medicine.
in Seminars in fetal & neonatal medicine
Description | International fellowship |
Amount | € 231,427 (EUR) |
Funding ID | PIEF-GA-2009-255578 |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 04/2010 |
End | 04/2012 |
Description | Elucidating the function of MPV17p |
Organisation | Newcastle University |
Department | Institute for Ageing and Health |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are studying the cell lines with methods and antibodies developed in-house |
Collaborator Contribution | The partners have provided cell lines from control subjects and patients with mitochondrial DNA depletion syndromes |
Impact | MPV17 regulates the nucleotide pool in mitochondria Publications in high impact journal |
Start Year | 2011 |
Description | Elucidating the function of MPV17p |
Organisation | Tsuyama Central Hospital |
Department | Department of Pediatrics |
Country | Japan |
Sector | Hospitals |
PI Contribution | We are currently studying the patient cell lines using methods and antibodies developed in house |
Collaborator Contribution | The collaborators has provided MPV17 patients material to validate my results |
Impact | Remodeling mtDNA associated proteins in absence of MPV17 |
Start Year | 2011 |
Description | Elucidating the function of MPV17p |
Organisation | University of Cambridge |
Department | Institute of Metabolic Science (IMS) |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are currently studying Mpv17 KO mouse tissues using methods and antibodies developed in house |
Collaborator Contribution | 1) The collaborator has helped to isolate tissues from Mpv17 KO mouse. 2) The Mpv17-/- mouse on the original background (CFW) has been back-crossed to C57Bl/J6 using the Marker-Assisted Accelerated Backcrossing (MAX-BAX®) provided by Charles River |
Impact | 1) Changes of mtDNA associated proteins in absence of Mpv17p 2) A KO models on a homogeneous inbred genetic background available for characterization. |
Start Year | 2011 |
Description | Elucidating the function of MPV17p |
Organisation | University of Oxford |
Department | Nuffield Department of Obstetrics & Gynaecology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are studying the cell lines with methods and antibodies developed in-house |
Collaborator Contribution | The partners have provided cell lines from control subjects and patients with mitochondrial DNA depletion syndromes |
Impact | MPV17 regulates the nucleotide pool in mitochondria Publications in high impact journal |
Start Year | 2011 |
Description | Metabolomics in Mpv17 KO mouse |
Organisation | University of Cambridge |
Department | Department of Biochemistry |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are providing samples from Mpv17 KO mouse and MPV17 overexpressing cell lines |
Collaborator Contribution | The collaborator has performed metabolite analysis in the Mpv17 mouse tissues. |
Impact | Altered metabolic profiles in the Mpv17 mouse tissues |
Start Year | 2011 |
Description | Mitochondrial dNTPs measurement |
Organisation | Vall d'Hebron University Hospital |
Country | Spain |
Sector | Hospitals |
PI Contribution | We have isolated mitochondria from Mpv17 KO mouse tissues and extract mitochondrial dNTP from the samples |
Collaborator Contribution | The collaborators have measured mitochondrial dNTP pools from Mpv17 KO mouse |
Impact | Imbalance of mitochondrial dNTPs pool in the absence of Mpv17. Paper in high impact journal |
Start Year | 2012 |