Endoplasmic Reticulum Stress Enhances Mitochondrial Metabolic Activity in Mammalian Adrenals and Gonads
| Autor: | James L. Thomas, Jasmeet Kaur, Amit V. Pandey, William E Burak, Anna N. Walker, Himangshu S. Bose, Guy Petruzzelli, Manoj Prasad, Shirley A. Powell, Randy M. Whittal |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Cytoplasm 3-Hydroxysteroid Dehydrogenases Mitochondrion Biology Mitochondrial Membrane Transport Proteins Phosphates Mice 03 medical and health sciences Stress Physiological Adrenal Glands Animals Translocase Gonads Molecular Biology Mammals 030102 biochemistry & molecular biology Endoplasmic reticulum Steroidogenic acute regulatory protein Articles Cell Biology Endoplasmic Reticulum Stress Phosphoproteins Mitochondria 030104 developmental biology Biochemistry Unfolded Protein Response Unfolded protein response biology.protein ATP–ADP translocase Intermembrane space Transcription Factor CHOP |
| Zdroj: | Molecular and Cellular Biology. 36:3058-3074 |
| ISSN: | 1098-5549 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|