--------------------------------------------------------------------------------
MitoNews
Mitochondrial Research Bulletin
Published by:
MitoSciences
Advancing Vital Discoveries in Mitochondrial Research
http://www.mitosciences.com
Edited by:
Dr. Roderick Capaldi
[email protected]
Volume 03, Number 02 - February, 2007
--------------------------------------------------------------------------------
Past Issues of MitoNews can be found at:
http://www.mitosciences.com/mitonews_archives.html
APOPTOSIS IS CON-FUSING: A TALE OF MITOCHONDRIAL MORPHOLOGY
In this Issue:
1. The "F" words.
2. Monitoring transient partial networks.
3. Mitochondrial trafficking in neurons.
4. The link between mitochondria movement and energy needs.
5. Mitochondrial distribution by GTPase RhoA.
6. Mitochondrial morphology changes link to PARL.
7. Puf3p another player in mitochondrial morphology.
8. Lymphocyte migration is correlated with mitochondrial movements.
9. NO fissions.
10. Stop fissioning and you'll live longer.
--------------------------------------------------------------------------------
1. The "F" words.
-----------------------------
Many of the cell biology and biochemistry textbooks still describe
mitochondria as bean-shaped organelles distributed around the
cytosol. We mitochondriacs know differently. In the last few
years it has been firmly established that mitochondria are highly
pleotropic and dynamic, switching between fragmented and
reticular morphologies depending on cell type, cell cycle, cell
stress, and other stimuli. A growing number of problems are now
known to control the organelle morphology by promoting fission
or fusion, and in many cases the mechanism or their activity has
been elucidated. While the ‘how’ of fission and fusion has
progressed rapidly, the ‘why’ has been less tractable. Is the
process designed to intermix and thereby allow complementation
of defective components, given that mutated mt DNAs are
inherited along with “wild type”? Does a dynamic structure allow
the organelle to migrate and service regions of the cell where
energy is most needed at any one time? Possibly both ideas are
correct. What we do know now is that there is an important
relationship between mitochondrial fission and fusion and
apoptosis. This, in turn, focuses attention on the link between
mitochondrial morphology and many human diseases including
neurodegeneration and cancer.
Recent developments and perspectives on the link between
mitochondrial fission and fusion and diseases are the subject of
several recent reviews, each with a slightly different focus, and
each worth reading to get the full overview.
A flood of reviews in a field can mean one of two things; the
protagonists have run out of good ideas for experiments, or the
field is moving very, very quickly. With respect to mitochondrial
fission and fusion, the latter is the case and there are several
interesting advances to report:
“Mitochondrial fusion and fission in mammals,” CHAN DC. Ann.
Rev. Cell Dev. Biol. 22. 79-99. (2006).
“Mitochondrial morphology and distribution in mammalian cells,”
FRAZIER AE, KIU C, STOJANOVSKI D, HOODENRADD NJ,
RYAN MT. Biol. Chem. 387: 12. 1551-8. (2006)
“Mitochondrial fragmentation in apoptosis,” ARNOULT D.
Trends in Cell Biol. 17:1. 6-12. (2007).
“The many shapes of mitochondrial death,” CEREGHETTI GM,
SCORRANO L. Oncogene. 25:34. 4717-24. (2006).
“Dysregulation of mitochondrial fusion and fission: an emerging
concept in neurodegeneration,” FRANK S. Acta. Neuropathol.
(Berl). 111:2. 93-100. (2006).
“Mitochondrial trafficking and morphology in healthy and injured
neurons,” CHANG DT, REYNOLDS IJ. Prog. Neurobiol. 80:5.
241-68. (2006).
2. Monitoring transient partial networks.
--------------------------------------------------------
Examination of the dynamics of the mitochondrial reticulum shows
continuous changes in connectivity so that there are transient
partial networks being created and broken down continually.
Monitoring the properties of these transient networks requires fast
kinetic analysis. This has now been accomplished by Ting et. al.
using mitochondrial matrix-targeted, photoactivatable, green
fluorescent protein. Using this approach with real time
monitoring, the authors were able to show that closely inter-twined
networks existed with separate properties. Each distinct network
was equi-potential based on membrane potential measurements.
Fusion and fission was found to occur without gross morphological
changes or fragmentation.
“Tagging and tracking individual networks within a complex
mitochondrial web with photoactivatable GFP,” TWIG G, GRAF
SA, WILSTROM JD, MOHAMED H, HAIGH SE, ELORZA A,
DEUTSCH M, ZURGIL N, REYNOLDS N, SHIRIHAI OS. Am.
J. Physiol. Cell Physiol. 291:1. C176-84. (2006).
3. Mitochondrial trafficking in neurons.
------------------------------------------------------
We now know that the distribution and dynamics of mitochondria,
whether in the fragmented or reticular form, is linked to
microfilaments and actin. The movements of the organelle along
these tracks can be visualized best in elongated cells such as
neurons. An elegant study of mitochondrial trafficking within
neurons and through dendrites to and from the synapse has been
described recently by Reynolds and colleagues. This work shows
selective cessation of mitochondrial movements in dendrites,
which might relate to early events in neural degeneration.
“Mitochondrial trafficking in synapse in cultured primary cortical
neurons,” CHANG DT, HONICK AS, REYNOLDS IJ. J.
Neurosci. 26:26. 7035-45. (2006).
4. The link between mitochondrial movement and energy needs visualized.
---------------------------------------------------------------------------------------------------
What signals mitochondria to move? An obvious possibility is
ATP needs. In a recent paper by Mironov, mitochondria were
visualized in neurons using TMRE in single particle tracking
experiments while intracellular ATP levels were simultaneously
monitored (using luciferase). These studies show a direct link
between energy need in local areas of the cell and organelle
movements.
“ADP regulates movements of mitochondria in neurons,”
MIRONOV S. Biophys. J. (Feb. 2 2007. Ahead of Print).
5. Mitochondrial distribution by GTPase RhoA
----------------------------------------------------------------------
The control of mitochondrial distribution has also been studied
recently by Mini et. al. who show that this process is controlled by
the GTPase RhoA in concert with cytosolic formins.
“Regulation of mitochondria distribution in RhoA and formins,”
MININ AA, KULIK AV, GYOEVA FK, LI Y, GOSHIMA G,
GELFAND VI. J. Cell Sci. 119:4 659-70. (2006).
6. Mitochondrial morphology changes; link to PARL.
--------------------------------------------------------------------------
The number of proteins included in the remodeling of
mitochondrial morphology continues to increase. Another player
is the presenilin-associated rhomboid-like protein PARL.
Phosphorylation of this protein, along with its cleavage, regulate
fragmentation of the organelle.
“Phosphorylation and cleavage of presenilin-associated rhomboid-
like protein (PARL) promotes changes in mitochondrial
morphology,” JEYARAJU DV, XU L, LETELLIER MC,
BANDARU S, ZUNINO R, BERG EA, MCBRIDE HM,
PELLEGRINI L. Proc. Natl. Acad. Sci. USA. 103:49. 18562-7.
(2006).
7. Puf3p; another player in mitochondrial morphology.
--------------------------------------------------------------------------
How many of you are confused by the names of the multitude of
gene products involved in apoptosis? Sitting though a lecture on
the subject recently reminded me of trying to communicate in
morse code as a cub scout. To bid, bad, bax, bak, bim, fuzzy onion
Dnm, OPA, bcl2 etc etc now add Puf3p! This protein is a Pumilio
family member????, an RNA binding protein (so why are they not
called rnaps?). Puf3p binds preferentially to mRNAs for nuclear
encoded mitochondrial proteins at the cytosolic face of the outer
membrane. It is involved in both biogenesis and mitochondrion-
cytoskeletal interactions.
“Puf3p, the Pumilio family RNA binding protein, localizes to
mitochondria and regulates mitochondrial biogenesis and motility
in budding yeast,” GARCIA-RODRIQUEZ LJ, GAY AC, PON
LA. J. Cell Biol. 176:2. 197-207. (2007).
8. Lymphocyte migration is correlated with mitochondrial movements.
-------------------------------------------------------------------------------------------
Mitochondrial morphology must conform to, and be linked to,
changes in overall cell shape. In an interesting study, Campello
et. al. show that mitochondrial movements occur as a part of the
spatial and functional asymmetry required for lymphocytes to
migrate to inflamed tissues.
“Orchestration of lymphocyte chemotaxis by mitochondrial
dynamics,” CAMPELLO S, LACALLE RA, BETTELLA M,
MANES S, SCORRANO L, VIOLA A. J. Exp. Med. 203:13.
2879-86. (2006).
9. NO fissions.
--------------------------
Two important recent papers link nitric oxide production to
mitochondrial fission, apoptosis, and neurodegeneration. They
show that nitric oxide evokes rapid mitochondrial fission in
cortical neurons by directing Bax to large foci on mitochondrial
fission sites, arguing that persistent fission of the organelle is an
early and casual event in NO-mediated neurotoxicity.
“Nitric oxide-induced mitochondrial fission is regulated by
dynamin-related GTPases in neurons,” BARSOUM MJ and 17
others. EMBO J. 25:16. 3900-11. (2006).
“Mitochondrial fission is an upstream and required event for bax
foci formation in response to nitric oxide in cortical neurons,”
YUAN H, GERENCSER AA, LIOT SA, ELLISMAN M,
PERKINS GA, BOSSY-WETZEL E. Cell Death Differ. (Oct. 20
2006 – Ahead of Print).
10. Stop fission-ing and you’ll live longer.
-------------------------------------------------------------
From the above it might seem that we could all live longer if we
reduce our mitochondrial fission. If you are a Podospora amserina
or a common yeast (S. cerevisiae) take comfort; it is true!
“Reducing mitochondrial fission results in increase life span and
fitness of two fungal ageing models,” SCHECKHUBER CQ,
ERJAVEC N, TINAZLI A, HAMANN A, NYSTROM T,
OSIEWACZ HD. Nat. Cell Biol. 9:1. 99-105. (2007).
--------------------------------------------------------------------------------
MitoNews is a publication of MitoSciences
http://www.mitosciences.com
To subscribe to MitoNews please go to:
http://www.mitosciences.com/mitonews.html
To unsubscribe please send a message to:
[email protected]
© Copyright 2004-2007 MitoSciences, Inc.
--------------------------------------------------------------------------------
