Resources > MitoNews > Archives > Volume 02, Number 04 - November, 2006

Volume 02, Number 04 - November, 2006




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MitoNews
Mitochondrial Research Bulletin

Published by:
MitoSciences
Advancing Vital Discoveries in Mitochondrial Research
http://www.mitosciences.com

Edited by:
Dr. Roderick Capaldi
rcapaldi@mitosciences.com

Volume 02, Number 04 - November, 2006
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Past Issues of MitoNews can be found at:
http://www.mitosciences.com/mitonews_archives.html


In this Issue:

In this Issue:

1. A mitochondria phospholipase involved in apoptosis.

2. More on phospholipases and mitochondria.

3. More on apoptosis: TOM22 the mitochondrial receptor for Bax.

4. Even more on apoptosis: glyceraldehydes-3-phosphate
dehydrogenase (GAPDH) a pro-apoptotic protein?

5. Why are diseases of Oxidative Phosphorylation tissue-specific?
One answer!

6. Defects of complex V, the ATP synthase; there's more than
just mtDNA mutations.

7. Transglutaminase and mitochondrial OXPHOS functioning.

8. Supersizing; Keep Up.

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Isn't it fun to be working on mitochondria. Lots of exciting basic
questions to answer, electronic devises and rotary-based motors
to be developed using principles first worked out by mitochondria,
and, diseases galore to understand and cure. We even get
ăpressä in Time magazine (Oct 9. 2006); soon our best may feature
in People magazine or on Dancing with the Stars.

In the mean time there are many exciting developments to report
occurring in the last few months.


1. A mitochondria phospholipase involved in apoptosis.

Two recent studies have localized a calcium independent
phospholipase A2 to mitochondria and claim that the enzyme
is involved in ărepair of oxidatively -modified cardiolipin, thereby
helping protect cells from oxidative stress mediated cell death.

SELEZNEV.K,ZHAO.C, ZHANG.XH, SONG.K &MA.ZA.
Calcium-independent phospholipase A2 localizes in and protects
mitochondria during apoptotic induction by staurosporine.
J.Biol.Chem. 281. 22275-88 (2006)

KINSEY.GR, McHOWAT.J, BECKETT.CS & SCHNELLMANN.R.
Identification of Calcium-independent phospholipase gamma
in mitochondria and its role in mitochondrial oxidative stress.
Am.J.Physiol.Renal Physiol. Oct 17 2006.


2. More on phospholipases and mitochondria.

Mitochondrial fusion is much more poorly understood than fission.
It is mediated by mitofusin but a role for fusogenic lipids such as
phosphatidic acid has not been shown. Choi et al. now describe
a phospholipase targeted to the mitochondrial outer membrane
that promotes mitofusin mediated fusion by hydrolyzing cardiolipin
to generate phosphatidic acid.

CHOI.SY, HUANG.P, JENKINS.GM, CHAN.DC, SCHILLER.J &
FROHMAN.MA.
A common lipid links MfN-mediated mitochondrial fusion and
SNARE regulated exocytosis.
Nat Cell Biol. 8. 1255-62 (2006)


3. More on apoptosis: TOM22 the mitochondrial receptor for Bax.

How does Bax interact with the mitochondrial outer membrane?
Add another proposal. Bellot et al. identify TOM22 as a (the)
receptor for Bax based on two hybrid studies in yeast. By peptide
mapping they find that the so called pore forming part of Bax (2
central alpha helices) is involved in the interaction. Further the
authors show that antisense knockdown of TOM22 inhibited the
interaction of Bax.

BELLOT. G. and 9 others.
TOM22, a core component of the mitochondria outer membrane
translocation pore, is a mitochondrial receptor for the proapoptotic
protein Bax.
Cell Death differ. Nov 10 (2006)


4. Even more on apoptosis: glyceraldehydes-3-phosphate
dehydrogenase (GAPDH) a pro-apoptotic protein?

Where will it stop; pleotropic proteins galore involved in apoptosis!
Cytochrome c·o.k. bid bad bim box bus etc!!! but GAPDH!!!
Tarze et al report that GAPDH accumulates in mitochondria during
apoptosis and interacts with porin but not ANT to mediate a
cyclosporin A inhibitable permeability pore transition. This leads to
release of cytochrome c and AIF.

TARZE and 9 others.
GAPDH, a novel regulator of the pro-apoptotic mitochondrial
membrane permeabilization.
Oncogene.Oct30 (2006)


5. Why are diseases of Oxidative Phosphorylation tissue-specific?
One answer!

We are used to thinking about the tissue specificity of the many
different OXPHOS deficiencies in terms of heteroplasmy, variable
distribution of mutated DNA's and threshold effects. In an elegant
study Shoubridge and colleagues add another variable; this time
different tissue expression of a nuclear encoded gene; in this
example the gene for the mitochondrial translation elongation
factor EFG1. By using blue native gel electrophoresis the authors
were able to show unique tissue-specific patterns of assembly of the
OXPHOS complexes in patients with mutations in EFG1. These
patients who died of liver failure showed the most reduction in
amount of complexes I and IV (10% residual) in liver but there
was near normal levels of the complexes in heart. It was shown
that these altered levels of OXPHOS complexes paralleled the
steady state levels of EFG1.

ANTONICKA.H, SASARMAN.F, KENNAWAY NG & SHOUBRIDGE.EA.
The molecular bassis for tissue specificity of the oxidative
phosphorylation deficiencies in patients with mutations in the
mitochondrial translation factor EFG1
Hum. Mol. Genet. 15. 1835-46 (2006)


6. Defects of complex V, the ATP synthase; there's more than
just mtDNA mutations.

As the number of reports of OXPHOS deficiency grows, it is
becoming clearer that while most pathological mutations are in
mtDNA, there are cases where nuclear genes are involved.
A recent paper by Sperl et al. describes 14 cases with isolated
deficiency of the mitochondrial ATP synthase caused by nuclear
genetic defects. They show that the phenotype of this set of
patients is significantly different from that of patients in which the
defect is in the mitochondrially encoded ATPase6 gene.

SPERL and 14 others.
Deficiency of mitochondrial ATP synthase of nuclear genetic origin.
Neuromuscul. Disord. Oct 16 (2006).


7. Transglutaminase and mitochondrial OXPHOS functioning.

Two recent papers by the Piacentini group focus attention on
the role that transglutaminase plays in the assembly of the
OXPHOS complexes through its function as a protein disulphide
isomerase. Mice lacking TG2 were shown to exhibit impairment
in OXPHOS and it was suggested that the enzyme does this by
modulating the formation of prohibitin complexes. In brain of the
transglutaminase- knockout mice there is a greatly reduced level
of complex I but higher levels of complex II. These mice were
less vulnerable to the effects of MPTP but more vulnerable to
3-nitropropionic acid. By proteomic analysis, the authors showed
that F1beta and prohibitin are substrates for transglutaminase.

MASTROBERARDINO. PG, FERRACE.MG, VITI.I, PAVONE.F,
FIMIA.GM, MELINO.G, RODOLFO.C & PIACENTINI.M.
Tissue transglutaminase contributes to the formation of disulphide
bridges in proteins of the respiratory complexes.
Biochim. Biophys. Acta. 1757. 1357-65 (2006)

BATTAGLIA and12 others.
Transglutamiinase 2 ablation leads to defective function of
mitochondrial respiratory chain complex I affecting neuronal
vulnerability in experimental models of extrapyramidal disorders.
J. Neurochem Oct25 (2006).


8. Supersizing; Keep Up.
The findings on interactions between OXPHOS complexes come
regularly. If like me you cannot keep up, there is a good review in
press and available on line.

BOEKEMA. EJ & BRAUN. H-P
Supramolecular structure of the mitochondrial oxidative
phosphorylation system.
J.Biol.Chem. 281 Nov13 (2006)



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