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The mitochondrial content of a cell is regulated by tissue specific endocrine and
physiologic signals so that it closely
matches the specific energetic needs faced by a cell.
This talk will focus on the transcriptional networks that communicate
tissue and physiologic state specific signals
to the regulation of mitochondrial biogenesis,
with an emphasis on recently identified components of the network,
namely the transcriptional coactivators,
PGC-1 alpha and PGC-1 beta,
and the PGC-1 effector estrogen related receptor alpha.
Biogenesis of mitochondria is a complex process,
requiring the coordinated transcription with close to
a thousand nuclear genes encoding mitochondrial proteins,
which I will loosely refer to as mitochondrial genes,
as well as their application and transcription of the mitochondrial DNA genome,
the biosynthesis of mitochondrial membranes,
and the import and assembly of the newly made proteins
and lipids to a functional and dynamic organelle.
The seemingly distinct processes have to be coregulated.
To a large extent, this coregulation is managed at the level of
transcriptional controlling the nucleus,
which determines the expression levels of mitochondrial components,
as well as directs the expression of regulators
of particular aspects of mitochondrial biogenesis.
For example, regulators of mitochondrial DNA replication and transcription,
as discussed by Richard Scarpulla in this series.
Besides determining the appropriate mitochondrial mass for the cell,
transcriptional regulation in the nucleus is also
specifying the structural and functional properties of the organelle.
Close to 60 percent of mitochondrial proteins are
differentially expressed in different tissues or in response to physiologic signals.
This differential expression reflects the role of mitochondria not just for
substrate oxidation and ATP production but also for other processes,
such as apoptosis, ion homeostasis,
signaling via production of reactive oxygen species,
thermogenesis, or steroid biosynthesis.
Elucidating the transcriptional networks that control mitochondrial biogenesis and
function is important for understanding
the mechanisms that may underlie mitochondrial diseases,
as well as for enabling strategies that may counteract such diseases.
Before reviewing the transcriptional regulators of mitochondrial biogenesis,
I will give you a brief and basic introduction to
the principles that govern regulation of gene expression.
Transcription factors recognize and bind directly to