2. • “powerhouse of the cell”
• ATP synthesis - production of energy during
the production of ATP
• Production of Heat – non-shivering
thermogenesis
• Role in apoptosis – programmed cell death
m.ivyroses.com/Biology/organelles/Function-of-Mitochondria.ph.
3.
4. • Examining the tragedies of several
families who each lost multiple
children, two teams of researchers
reveal a previously unappreciated
role for a mitochondrial enzyme.
5. • Jeanne Amiel, a genetics researcher at the
French Institute of Health and Medical
Research (INSERM) in Paris, searching for
answers.
6. • One set of parents had lost four babies, each
suddenly and unexpectedly, one after
another—all of the children were between 14
months and 15 months old.
• The other parents had suffered the deaths of a
20-month-old and, later, a four-month-old. In
each case, the babies’ hearts stopped, but no
one knew why.
7. • The parents whose fourth toddler died even
took the child in for monthly check-ups
with a cardiac specialist to be sure nothing
would be overlooked.
• A 15-year-old boy took a sip of beer,
collapsed, and died. Several years later, his
then 20-year-old brother suffered the same
consequence after drinking a small amount
of alcohol.
8. • Amiel’s team and another led by Peter
George of the University of Otago
and Johannes Mayr of Paracelsus
Medical University Salzburg in Austria
finally have answers for these families.
9. • The researchers independently pinpointed the
cause of the kids’ deaths to inherited
mutations in a single gene, PPA2, which codes
for a mitochondrial enzyme.
10. • It’s the first time this gene has been
implicated in disease. “It was not known to be
so important to the cell before this study,”
Amiel told The Scientist. “This was not
expected.”
• Given the patterns within the families who
had approached her (there were no sudden
deaths among babies of other generations,
and the fatalities affected both boys and girls),
Amiel suspected that the children carried the
same autosomal recessive mutation.
11. • conducted whole-exome sequencing on some
of the victims, which led them to PPA2, whose
protein is the mitochondrial inorganic
pyrophosphatase (another inorganic
pyrophosphatase is present in the cytosol).
The enzyme catalyzes the production of
orthophosphate from inorganic
pyrophosphate, a reaction important for the
production of DNA, RNA, and other
biomolecules.
12. • The researchers expressed these mutant
sequences in yeast, finding that they crippled
the microbes' growth. Completely wiping out
the Ppa2 protein prevented the yeast from
growing at all.
13. • identified mutations are extremely detrimental to
mitochondrial maintenance and function
• It’s not clear how that ultimately leads to cardiac
arrest, but the researchers noted that they
suspect the heart becomes poisoned by inorganic
pyrophosphate.
• As a result:
“mitochondria can no longer supply energy to the
cell”
14. • Mayr's group similarly arrived at PPA2 in its
analysis of four families with kids who died of
cardiac arrest: the family who lost the two
brothers, plus one family who lost three
newborns, a family whose children died at five
months and 11 months of age, and a fourth
family whose two-year-old died.
• In these cases, however, the clinical experiences
were different. With the brothers there was their
comparatively older age and alcohol sensitivity,
and two of their siblings—who also carry the
same PPA2mutations—are still alive in their 30s
and wearing pacemakers.
15. Another study of Mayr is also health study for
children such as seizures and elevated plasma
lactate levels.
It shows mitochondrial disorders can be
extremely heterogeneous,” said Pankaj Agrawal,
a neonatologist at Boston Children’s Hospital
who investigates unexplained deaths in
newborns.
16. • Agrawal said it’s possible that some of his
patients’ fatalities may be explained
by PPA2 variants. However, these rare
mutations will not account for most sudden
infant deaths, said Amiel, and screening for
them should be limited to families who have
experienced a child’s death by sudden cardiac
arrest and have other reason to
suspect PPA2 might be involved. For instance,
some of the victims showed signs of cardiac
dysfunction upon histological examination
17. • Amiel pointed out that most of the children in the
two studies would not technically be considered
SIDS cases because they were over 12 months of
age. Weese-Mayer said the papers strengthen the
argument that doctors looking into a SIDS event
should ask about family history beyond the
sudden death of babies to family members of all
ages.
• http://www.the-scientist.com/?articles.view/articleNo/46765/title/Kids--Sudden-Cardiac-Deaths-
Explained-by-Heritable-Mutations-in-a-Single-Gene/
