Radovic 2019a MiP2019

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Sava Radovic
Conditional deletion of insulin and IGF1 receptors in steroidogenic cells changes profile of molecular markers of mitochondrial dynamics in myocard of prepubertal male, but not female mice.

Link: MiP2019

Radovic SM, Starovlah IM, Nef S, Kostic TS, Andric SA (2019)

Event: MiP2019

COST Action MitoEAGLE

Mitochondria are essential for cardiac function since they produce ATP and other essential cellular mitocrine signals, store and buffer calcium, initiate cell death signals, etc. Not surprisingly, mitochondrial dysfunction has been linked to several severe cardiovascular disorders. The contribution of cellular signaling is required for heart homeostasis, but link between them and mitochondrial dynamic is not described well. We used prepubertal male and female mice with insulin/IGF1 receptors deletion in steroidogenic cells (Insr/Igf1r-DKO) to determine the transcription profile of markers of mitochondrial dynamics in myocard, since these mice have decreased level of circulating-sex-steroid-hormones.

In order to determine relative expression of the genes coding mitochondrial dynamics markers, total RNA was isolated from mouse myocard, first strand cDNA was synthesized and polymerase chain reaction in real time (RQ-PCR) was preformed.

RQ-PCR-results revealed increased transcription of Ppargc1a, the master regulator of mitochondrial dynamics and integrator of environmental signals, as well as his downstream targets Pparg and Nrf1 in hearts of Insr/Igf1r-DKO males, but not females, comparing to controls. The marker of mitochondrial fusion/architecture, Opa1, decreased in hearts from Insr/Igf1r-DKO males, but not females, while Mfn1/Mfn2 remained unchanged in mice of both sexes. The transcription of the main markers of mitophagy (Pink, Prkn) remained unchanged in mice of both sexes, while transcript for Tfeb (master gene involved in autophagy) declined in hearts of both sexes. This was followed by decreased mtDNA copy numbers in hearts of Insr/Igf1r-DKO males, but increased in females, suggesting the importance of sex-steroid- hormones in regulation of mtDNA copy numbers.

According to our best knowledge, these results are the first data showing the transcriptional profile of mitochondrial dynamics markers in myocard of prepubertal mice and can be used as a solid base for further research.


Bioblast editor: Plangger M, Tindle-Solomon L


Labels: MiParea: nDNA;cell genetics, Genetic knockout;overexpression, Gender 


Organism: Mouse  Tissue;cell: Heart 





Affiliations and support

Radovic SM(1), Starovlah IM(1), Nef S(2), Kostic TS(1), Andric SA(1)
  1. Lab Reproductive Endocrinology Signaling, Lab Chronobiology Aging, Centre Excellence CeRES, Fac Sciences, Univ Novi Sad, Novi Sad, Serbia
  2. Lab Molecular Developmental Biology Sexual Development, Univ Geneva, Geneva, Switzerland. – [email protected]
This work was supported by the grant no. 173057 and grant no. 451-0302807 Centre of Excellence CeRES from the Ministry of Education, Science and Technological Development, Republic of Serbia, grant no. 2130 from the Autonomous Province of Vojvodina as well as grant no. IZ73Z0-128070 from Swiss National Science Foundation.