Mracek 2017 MiP2017

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Mracek Tomas
Knockout of DAPIT, an accessory subunit of mitochondrial ATP synthase, causes right ventricular hypertrophy and pulmonary hypertension.

Link: MiP2017

Pecina P, Nuskova H, Kovalcikova J, Zidek V, Landa V, Kaplanova V, Kolar F, Papousek F, Sedmera D, Kazdova L, Bardova K, Flachs P, Tauchmannova K, Drahota Z, Kopecky J, Pravenec M, Houstek J, Mracek T (2017)

Event: MiP2017

COST Action MITOEAGLE

FoF1-ATP synthase is the key enzyme of mitochondrial energy provision, responsible for production of most of the cellular ATP. Recently, small proteolipid DAPIT (also termed Usmg5) of 7 kDa has been found to be loosely attached to the enzyme, but its biological role is largely enigmatic. To elucidate the importance of this protein we produced ZFN rat knockout model of DAPIT deficiency on SHR background. DAPIT-/- animals were fully viable and contrary to previous data on cell lines, we observed normal levels of assembled ATP synthase. ATP synthase was slightly more labile, but complete and functional. Both ADP phosphorylating and hydrolysing activities were reduced by circa 10% in both liver and heart. DAPIT -/- animals had 20-30% lower body weight and pronounced decrease in total adiposity (by 40%). This was accompanied by general improvement of metabolic phenotypes and better peripheral insulin sensitivity. Contrasting with metabolic data, we observed selective hypertrophy of right ventricle (RV) accompanied by an increase in right ventricular systolic pressure (RVSP). RVSP in DAPIT-/- animals was positively correlated with RV mass (r2=0.53). Concomitantly, we observed higher calcium retention capacity in heart mitochondria from DAPIT-/- animals, suggestive of higher resistance against induction of apoptosis in such cells. In conclusion, absence of DAPIT protein leads to mild decrease in mitochondrial ATP synthase function which manifests as decreased total adiposity and improved insulin sensitivity but also leads to the development pulmonary hypertension in rat.


Bioblast editor: Beno M, Kandolf G O2k-Network Lab: CZ Prague Houstek J, CZ Prague Kopecky J


Labels: MiParea: Genetic knockout;overexpression 


Organism: Rat  Tissue;cell: Heart, Liver 





Affiliations and support

Pecina P(1), Nuskova H(1), Kovalcikova J(1), Zidek V(1), Landa V(1), Kaplanova V(1), Kolar F(1), Papousek F(1), Sedmera D(1), Kazdova L(2), Bardova K(1), Flachs P(1), Tauchmannova K(1), Drahota Z(1), Kopecky J(1), Pravenec M(1), Houstek J(1), Mracek T(1)
  1. Inst Physiology, Czech Acad Sc
  2. Inst Clinical and Experimental Medicine, Prague, Czech Republic – tomas.mracek@fgu.cas.cz
This project is supported by the Czech Science Foundation grant 14-36804G.