|
| |
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online April 18, 2008
Journal of Experimental Biology 211, i-a (2008)
Copyright © 2008 The Company of Biologists Limited
doi: 10.1242/jeb.019174
Inside JEB |
DIVISION OF LABOUR IN GOLDFISH METABOLIC REMODELLING
kathryn{at}biologists.com
Mitochondria are the tiny cellular energy factories, fuelled by fats and
sugars, which produce the ATP that powers most life on our planet. And when
animals' metabolic demands increase, their mitochondrial levels rise to
satisfy their increasing ATP demands. Chris Moyes, from Queen's University,
Canada, explains that the key molecular components that control mitochondrial
levels in mammals are well understood, but how mitochondrial proliferation is
regulated in lower vertebrates was less clear. According to Moyes, the PPAR
gamma coactivator (PGC-1) family of proteins are the `master regulators' of
mitochondrial synthesis in mammals. They work in conjunction with other
transcription factors, such as NRF-1 to control mitochondrial gene expression,
and PPAR to regulate the mitochondrion's fuel choice. Teaming up with
Christophe LeMoine and Christine Genge, Moyes decided to find out whether
PGC-1
and PGC1-β are also key players in the metabolic remodelling
of a more `comparative' model; the goldfish
(p. 1448). According
to Moyes, fish respond to cold in the same way that animals respond to
endurance training; their mitochondrial levels rise. So if he wanted to
identify key cellular factors involved in mitochondrial proliferation during
metabolic remodelling, all he'd have to do was maintain fish at different
temperatures for several weeks as they adjusted their mitochondrial levels,
and track the expression of remodelling related genes to identify the key
transcriptional regulator. The goldfish was the obvious candidate, surviving
temperatures that other model species can't tolerate.
Having kept the fish at 4, 20 and 35°C for 3 weeks, the team collected
heart, muscle and liver samples and measured the mRNA levels of PGC-1,
PGC-1β, and the PPAR and NRF-1 transcription factors; key factors known
to be involved in mammalian mitochondrial synthesis. LeMoine and Genge also
measured the mRNA and enzyme activity levels of three major mitochondrial
metabolic proteins (citrate synthase and two cytochrome oxidase subunits I and
IV), to see if they correlated with PGC-1 expression levels.
But the team was in for a surprise. PGC-1 levels did not rise as
mitochondrial gene expression increased in response to the cold; they
plummeted. And when the team compared both PGC-1 transcript levels with the
expression of mitochondrial genes and NRF-1 they found that PGC-1β was
the protein regulating mitochondrial synthesis. So PGC-1β, and not
PGC-1, is the master regulator of mitochondrial synthesis in
goldfish.
Knowing that animals also remodel mitochondria depending on which fuel they
consume, the team fed fish on high fat, low fat and restricted diets to see
how PGC1 regulated mitochondrial gene expression. This time PGC1 levels
rose in line with the PPAR transcription factor, which regulates fat
metabolism, suggesting that PGC1 has a role in setting the
mitochondria's fuel preference.
So, unlike mammals, where metabolic remodelling is controlled by the
PGC-1 master regulator, fish have opted for a division of labour
scheme, with individual PGC-1 proteins responsible for different aspects of
the remodelling response to altered metabolic demands.
References
LeMoine, C. M. R., Genge, C. E. and Moyes, C. D.
(2008). Role of the PGC-1 family in the metabolic adaptation of
goldfish to diet and temperature. J. Exp. Biol.
211,1448
-1455.
Related articles in JEB:
| ||||||||||||||||||||||||||||||||||||||||||||
