Dataset Information

Mitochondrial dynamics in ovarian granulosa cells during follicular growth and in human KGN cells

ABSTRACT: In the ovary, proliferation and differentiation of granulosa cells (GCs) drive the growth of follicles. This is, in part, dependent on gonadotropins. Our immunohistochemical studies provided hints of mitochondrial biogenesis and intracellular redistribution in GCs of growing follicles. A cellular model, human KGN cells (granulosa cell tumor cells, derived from growing follicles) was used to study aspects of mitochondrial dynamics. To elevate cAMP and thereby mimic gonadotropin actions, forskolin (FSK) was used, which increased KGN cell size and mitochondrial DNA within 24 h. MitoTracker experiments and ultrastructural 3D reconstruction revealed that FSK treatment induced the formation of elaborate mitochondrial networks. H89, a protein kinase A (PKA) inhibitor, reduced network formation. A proteomic analysis indicated that FSK among others elevated levels of regulators of the cytoskeleton and the steroidogenic enzyme CYP11A1, located in mitochondria, was more than 3-fold increased, implying that cAMP/PKA-associated structural changes go in parallel with the acquisition of steroidogenic competence of mitochondria in KGN cells. In summary, in situ observations showed increases in mitochondria and suggested intracellular trafficking in GCs during follicular growth and indicated that they may partially be under the control of gonadotropins/cAMP. In line with this, elevation of cAMP in KGN profoundly affected mitochondria dynamics in a PKA-dependent manner and implicated cytoskeletal changes.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Kgn Cell

SUBMITTER: Ignasi Forne

LAB HEAD: Prof. Dr. med. Artur Mayerhofer

PROVIDER: PXD032160 | Pride | 2022-10-14

REPOSITORIES: Pride

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			Action	DRS
	Ref2116_MK_01_20190404.raw	Raw
	Ref2116_MK_02_20190404.raw	Raw
	Ref2116_MK_03_20190404.raw	Raw
	Ref2116_MK_07_20190404.raw	Raw
	Ref2116_MK_08_20190404.raw	Raw

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Publications

Evidence of a role for cAMP in mitochondrial regulation in ovarian granulosa cells.

Kaseder Melanie M Schmid Nina N Eubler Katja K Goetz Katharina K Müller-Taubenberger Annette A Dissen Gregory A GA Harner Max M Wanner Gerhard G Imhof Axel A Forne Ignasi I Mayerhofer Artur A

Molecular human reproduction 20220901 10

In the ovary, proliferation and differentiation of granulosa cells (GCs) drive follicular growth. Our immunohistochemical study in a non-human primate, the Rhesus monkey, showed that the mitochondrial activity marker protein cytochrome c oxidase subunit 4 (COX4) increases in GCs in parallel to follicle size, and furthermore, its intracellular localization changes. This suggested that there is mitochondrial biogenesis and trafficking, and implicates the actions of gonadotropins, which regulate fo ...[more]

PMID: 35944223

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