Characterization of the Effect of the Mitochondrial Protein Hint2 on Intracellular Ca2+ dynamics

Ndiaye, Dieynaba; Collado-Hilly, Mauricette; Martin, Juliette; Prigent, Sylvie; Dufour, Jean-François; Combettes, Laurent; Dupont, Geneviève (2013). Characterization of the Effect of the Mitochondrial Protein Hint2 on Intracellular Ca2+ dynamics. Biophysical journal, 105(5), pp. 1268-1275. Biophysical Society 10.1016/j.bpj.2013.06.048

[img] Text
Characterization of the Effect of the Mitochondrial Protein Hint2.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (597kB) | Request a copy

Hint2, one of the five members of the superfamily of the histidine triad AMP-lysine hydrolase proteins, is expressed in mitochondria of various cell types. In human adrenocarcinoma cells, Hint2 modulates Ca2+ handling by mitochondria. As Hint2 is highly expressed in hepatocytes, we investigated if this protein affects Ca2+ dynamics in this cell type. We found that in hepatocytes isolated from Hint2−/− mice, the frequency of Ca2+ oscillations induced by 1 μM noradrenaline was 150% higher than in the wild-type. Using spectrophotometry, we analyzed the rates of Ca2+ pumping in suspensions of mitochondria prepared from hepatocytes of either wild-type or Hint2−/− mice; we found that Hint2 accelerates Ca2+ pumping into mitochondria. We then resorted to computational modeling to elucidate the possible molecular target of Hint2 that could explain both observations. On the basis of a detailed model for mitochondrial metabolism proposed in another study, we identified the respiratory chain as the most probable target of Hint2. We then used the model to predict that the absence of Hint2 leads to a premature opening of the mitochondrial permeability transition pore in response to repetitive additions of Ca2+ in suspensions of mitochondria. This prediction was then confirmed experimentally.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology

UniBE Contributor:

Dufour, Jean-François

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0006-3495

Publisher:

Biophysical Society

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

16 Jun 2014 16:26

Last Modified:

06 Nov 2015 09:50

Publisher DOI:

10.1016/j.bpj.2013.06.048

BORIS DOI:

10.7892/boris.53732

URI:

https://boris.unibe.ch/id/eprint/53732

Actions (login required)

Edit item Edit item
Provide Feedback