Translational Regulation During Mitochondrial Biogenesis in Brown Adipogenesis

Author(s):  
Ip Jun Yu
Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Paul Huang ◽  
Sylvia Lee-Huang

Introduction: In addition to its roles as a vascular signaling molecule, nitric oxide (NO) plays roles in metabolism. Mice deficient in eNOS are overweight and develop insulin resistance. It is not known whether the metabolic effects are due to primary roles of NO, or to increased visceral adiposity, leading to secondary metabolic changes. Hypothesis: We hypothesized that NO plays distinct and separable primary roles in white and brown adipogenesis, which underlie the effects on adiposity, energy metabolism, and expression of thermogenic genes. Methods: We exposed wild-type and mice carrying specific gain of function and loss of function eNOS mutations to cold at 4C for 48 hours and assessed expression of thermogenic gene programs in white and brown adipose tissue. To study cell autonomous effects, we differentiated adipocyte precursors from brown and white fat in the presence of NOS inhibitors and NO donors, as well as with siRNA to knockdown eNOS expression. Results: Cold exposure resulted in upregulation of the thermogenic gene program in brown adipose tissue. Animals carrying a gain of function mutation in eNOS showed increased UCP1 expression even without cold exposure. Induction of thermogenic genes was more pronounced in the animals with gain of function eNOS mutation. Differentiation of adipocyte precursors showed effects of eNOS on adipogenesis. Cells treated with the pharmacologic blockade (L-NAME and L-NA) as well as genetic knockdown (siRNA) showed dose-dependent inhibition of adipocyte differentiation. MitoTracker Red CMXRos staining showed that treatment with the NO donor SNAP increases mitochondrial biogenesis, while L-NAME decreases mitochondrial biogenesis. Conclusions: We show that eNOS-derived NO plays distinct and separable roles in white and brown adipogenesis. In brown adipocytes, eNOS regulates the expression of the thermogenic gene program, with upregulation of expression even without cold exposure, and greater increase in response to cold. In white adipocytes, eNOS-derived NO is required for adipocyte differentiation and mitochondrial biogenesis.


2020 ◽  
Vol 295 (15) ◽  
pp. 5095-5109 ◽  
Author(s):  
Cyrielle L. Bouchez ◽  
Edgar D. Yoboue ◽  
Livier E. de la Rosa Vargas ◽  
Bénédicte Salin ◽  
Sylvain Cuvellier ◽  
...  

Heme (iron protoporphyrin IX) is a well-known prosthetic group for enzymes involved in metabolic pathways such as oxygen transport and electron transfer through the mitochondrial respiratory chain. However, heme has also been shown to be an important regulatory molecule (as “labile” heme) for diverse processes such as translation, kinase activity, and transcription in mammals, yeast, and bacteria. Taking advantage of a yeast strain deficient for heme production that enabled controlled modulation and monitoring of labile heme levels, here we investigated the role of labile heme in the regulation of mitochondrial biogenesis. This process is regulated by the HAP complex in yeast. Using several biochemical assays along with EM and epifluorescence microscopy, to the best of our knowledge, we show for the first time that cellular labile heme is critical for the post-translational regulation of HAP complex activity, most likely through the stability of the transcriptional co-activator Hap4p. Consequently, we found that labile heme regulates mitochondrial biogenesis and cell growth. The findings of our work highlight a new mechanism in the regulation of mitochondrial biogenesis by cellular metabolites.


Plant Science ◽  
1987 ◽  
Vol 51 (1) ◽  
pp. 61-76 ◽  
Author(s):  
Antonio F. Monroy ◽  
Susan A. McCarthy ◽  
Steven D. Schwartzbach

2020 ◽  
Vol 133 (18) ◽  
pp. jcs247593 ◽  
Author(s):  
Raja Gopal Reddy Mooli ◽  
Dhanunjay Mukhi ◽  
Zhonghe Chen ◽  
Nia Buckner ◽  
Sadeesh K. Ramakrishnan

ABSTRACTEmerging evidence indicates that proper mitochondrial dynamics are critical for adipocyte differentiation and functional thermogenic capacity. We found that the mitochondrial fission protein dynamin-related protein 1 (DRP1, also known as DNML1) is highly expressed in brown adipose tissue compared to expression in white adipose tissue, and these expression levels increase during brown adipocyte differentiation. Our results reveal that the inhibition of DRP1 using mdivi-1 mitigates beige adipocyte differentiation and differentiation-associated mitochondrial biogenesis. We found that DRP1 is essential for the induction of the early-phase beige adipogenic transcriptional program. Intriguingly, inhibition of DRP1 is dispensable following the induction of beige adipogenesis and adipogenesis-associated mitochondrial biogenesis. Altogether, we demonstrate that DRP1 in preadipocytes plays an essential role in beige and brown adipogenesis.This article has an associated First Person interview with the first author of the paper.


2016 ◽  
Vol 44 (6) ◽  
pp. 1717-1724 ◽  
Author(s):  
Yi Zhang ◽  
Hong Xu

Mitochondria are generated by the expression of genes on both nuclear and mitochondrial genome. Mitochondrial biogenesis is highly plastic in response to cellular energy demand, developmental signals and environmental stimuli. Mechanistic target of rapamycin (mTOR) pathway regulates mitochondrial biogenesis to co-ordinate energy homeostasis with cell growth. The local translation of mitochondrial proteins on the outer membrane facilitates their efficient import and thereby allows prodigious mitochondrial biogenesis during rapid cell growth and proliferation. We postulate that the local translation may also allow cells to promote mitochondrial biogenesis selectively based on the fitness of individual organelle. MDI–Larp complex promotes the biogenesis of healthy mitochondria and thereby is essential for the selective transmission of healthy mitochondria. On the other hand, PTEN-induced putative kinase 1 (PINK1)–Pakin activates protein synthesis on damaged mitochondria to maintain the organelle homeostasis and activity. We also summarize some recent progress on miRNAs' regulation on mitochondrial biogenesis.


2000 ◽  
Vol 24 (6) ◽  
pp. 805-813 ◽  
Author(s):  
Gorou Horiguchi ◽  
Takuichi Fuse ◽  
Naoto Kawakami ◽  
Hiroaki Kodama ◽  
Koh Iba

2014 ◽  
Author(s):  
Jessie M Sutherland ◽  
Alexander P Sobinoff ◽  
Kate Redgrove ◽  
Tara-Lynne Davidson ◽  
Nicole A Siddall ◽  
...  

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1966-P
Author(s):  
MENGISTU LEMECHA ◽  
KATSUTARO MORINO ◽  
TAKESHI IMAMURA ◽  
HIROTAKA IWASAKI ◽  
NATSUKO OHASHI ◽  
...  

2017 ◽  
Vol 95 (9) ◽  
pp. 4078 ◽  
Author(s):  
S. H. White ◽  
S. Wohlgemuth ◽  
C. Li ◽  
L. K. Warren

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