Endoplasmic Reticulum Stress Enhances Mitochondrial Metabolic Activity in Mammalian Adrenals and Gonads.

Prasad, Manoj; Walker, Anna N; Kaur, Jasmeet; Thomas, James L; Powell, Shirley A; Pandey, Amit Vikram; Whittal, Randy M; Burak, William E; Petruzzelli, Guy; Bose, Himangshu S (2016). Endoplasmic Reticulum Stress Enhances Mitochondrial Metabolic Activity in Mammalian Adrenals and Gonads. Molecular and cellular biology, 36(24), pp. 3058-3074. American Society for Microbiology 10.1128/MCB.00411-16

[img] Text
Mol. Cell. Biol.-2016-Prasad-3058-74.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (3MB) | Request a copy
[img]
Preview
Text
Mol. Cell. Biol.-2016-Prasad-MCB.00411-16.pdf - Accepted Version
Available under License Publisher holds Copyright.

Download (2MB) | Preview

The acute response to stress consists of a series of physiological programs to promote survival by generating glucocorticoids and activating stress response genes that increase the synthesis of many chaperone proteins specific to individual organelles. In the endoplasmic reticulum (ER), short-term stress triggers activation of the unfolded protein response (UPR) module that either leads to neutralization of the initial stress or adaptation to it; chronic stress favors cell death. UPR induces expression of the transcription factor, C/EBP homology protein (CHOP), and its deletion protects against the lethal consequences of prolonged UPR. Here, we show that stress-induced CHOP expression coincides with increased metabolic activity. During stress, the ER and mitochondria come close to each other, resulting in the formation of a complex consisting of the mitochondrial translocase, translocase of outer mitochondrial membrane 22 (Tom22), steroidogenic acute regulatory protein (StAR), and 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2) via its intermembrane space (IMS)-exposed charged unstructured loop region. Stress increased the circulation of phosphates, which elevated pregnenolone synthesis by 2-fold by increasing the stability of 3βHSD2 and its association with the mitochondrion-associated ER membrane (MAM) and mitochondrial proteins. In summary, cytoplasmic CHOP plays a central role in coordinating the interaction of MAM proteins with the outer mitochondrial membrane translocase, Tom22, to activate metabolic activity in the IMS by enhanced phosphate circulation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Endokrinologie / Diabetologie / Metabolik (Pädiatrie)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Tiefenau Hospital (discontinued) > Forschungsgruppe Endokrinologie/Diabetologie/Metabolik (Pädiatrie) (discontinued)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

UniBE Contributor:

Pandey, Amit Vikram

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0270-7306

Publisher:

American Society for Microbiology

Language:

English

Submitter:

André Schaller

Date Deposited:

22 May 2017 15:51

Last Modified:

23 May 2017 08:00

Publisher DOI:

10.1128/MCB.00411-16

PubMed ID:

27697863

BORIS DOI:

10.7892/boris.95631

URI:

https://boris.unibe.ch/id/eprint/95631

Actions (login required)

Edit item Edit item
Provide Feedback