Mitochondrial dysfunction in autism
Mitochondrial dysfunction with defects in oxidative phosphorylation
has been suspected in autism and several recent findings that
show abnormalities in mitochondrial enzyme activities that support
hypothesis. Postmortem examination of autistic brains revealed
significantly elevated calcium levels in autistic
brains compared to controls, followed by elevations of mitochondrial
aspartate/glutamate carrier rates and mitochondrial metabolism
and oxydation rates (18607376].
Disturbance of mitochondrial energy production in autism was
confirmed by another recent study .
(also see Brain Development and Oxydative Stress). also see
Brain Development and Oxidative
to controls autistic patients show significantly lower carnitine
levels, followed by elevated levels of lactate, aspartate aminotransferase,
creatine kinase and significantly elevated levels of alanine
and ammonia [16566887,
A pilot study investigating brain high energy phosphate and
membrane phospholipid metabolism in individuals with autism
found decreased levels of phosphocreatine and esterified ends
(alpha ATP + alpha ADP + dinucleotides + diphosphosugars) compared
to the controls. When the metabolite levels were compared with
neuropsychologic and language test scores, a common pattern
of correlations was observed across measures in the autistic
group, wherein as test performance declined, levels of high
energy phosphate compounds and of membrane building blocks decreased,
and levels of membrane breakdown products increased. The authors
concluded that the results of the study provided tentative evidence
of alterations in brain energy and phospholipid metabolism in
autism that correlate with the level of neuropsychologic and
language deficits 
(also see Membrane).
This was further confirmed by another study finding the impairment
of energy metabolism in autistic patients which could be correlated
to the oxidative stress (19376103).
Also see Oxidative Stress
Calcium homeostasis and mitochondria
One of the functions of mitochondria is to store free calcium.
Release of this stored calcium back into the interior of the
cell can initiate calcium spikes or waves. These events coordinate
various processes in different types of cells, for example neurotransmitter
release in nerve cells and release of hormones in endocrine
cells. Excess calcium ions stored in mitochondria can inhibit
oxidative phosphorylation. In the nerve cells this can causes
an irreversible reduction in the energy status of nerve terminals,
which can initiate pathophysiological processes in those cells.
Numerous findings have indicated a crucial role of calcium influx
through L-type calcium channels in mitochondrial calcium overload
and downstream mitochondrial and cellular dysfuctions. It has
been shown that blockade of LTCC in the plasma membrane not
only inhibits an increase in cellular calcium but also stabilizes
mitochondrial membranes calcium homeostasis and generation of
ROS by mitochondria [16760264,
In one study inhibition of calcium inward current with verapamil
protected against oxidative stress as well as morphological
changes and dysfunction of mitochondria 
are some indications that, simultanious to LTCC, N-methyl-D-aspartate
(NMDA) receptors are also involved in oxidative stress, mitochondrial
dysfunction, and ATP depletion mediated by calcium influx .
The involvement of LTCC in cellular and mitochondrial accumulation
of calcium has been demonstrated in vitro in hypoxic renal tubular
and in bovine chromaffin cells ,
showing that these channels play an important role in regulating
mitochondrial permeability transition, cytochrome c release,
caspase activation, and ATP depletion-induced mitochondrial
apoptosis. The reduced efficiency of handling of intracellular
calcium loads in neurons may be an important factor contributing
to the onset of neuronal damage during hypoxia and ischaemia
Calcium influx through LTCC is involved in the ischemic damage
in neonatal brain which manifests itself as a decrease in the
energy state, with decreased levels of phosphocreatine and ATP,
and an increases in lactate 
At the same time deenergization of mitochondria affects the
cellular calcium influx rate .
Several inherited human encephalomyopathies exhibit neurological
symptoms, including autism-related symptoms, in association
with specific mitochondrial mutations .
It can therefore be proposed that this inability to regulate
calcium influx and homeostasis is one of the probable mechanisms
behind increased neuronal vulnerability and subsequent development
of autistic-like behavioural symptoms in human encephalomyopathies.