Mitochondria as the motors of consciousness

Andrew Gyles syzygium at alphalink.com.au
Wed Nov 29 20:50:53 EST 2000

Mitochondria as the motors of consciousness

I suggest that the reason why mitochondria have retained some protein-
coding genes is that these genes code for proteins that determine,
indirectly or directly, the frequencies of rotation of the
ATPsynthase/ATPase enzymes in the mitochondrial cristae. I propose here
that these frequencies determine the characteristic single frequencies
of 'firing' of various neurons that are important to particular aspects
of consciousness.

If these genes had been transferred to the nucleus each of them would
have become paired (one on each homologous chromosome). Then they would
probably have mutated into functional but non-identical alleles. These
alleles could be variously expressed in the mitochondria of each cell.
Each cell would then contain mitochondria that rotated at different
frequencies in the same circumstances. This could cause the neurons to
be triggered at two or more frequencies, and so cause the loss of the
aspect of consciousness for which each group of neurons was responsible.

I propose that if mitochondrial DNA were inherited biparentally similar
multi-frequency confusion would be caused in the neurons.

An explanation of my hypothesis

In certain circumstances a mitochondrion will oscillate (rather like
the crystal oscillators used in elctronic circuits) because 'hydraulic
interference'  between neighbouring F1 units of ATPsynthase/ATPase
arranged in almost crystalline fashion on the cristae will force all
the units to rotate synchronously and in phase. They will therefore
rotate like the dynamos of a national electricity generating network,
which all run synchronously and in phase.

As an example of strict 'hydraulic interference' consider the actions
of two divers reaching a completely flooded submarine and entering it,
one from the stern and the other from the bow. They reach a central
compartment with a door at each end. Each door can be opened inward or
outward. They wish to enter this flooded compartment. If they try to
open both doors inward simultaneously they will fail. If they try to
open both doors outward simultaneously they will fail. But if one diver
opens his door inward and the other diver opens his door outward they
will succeed. This is because water is practically incompressible and
inexpandable, except for the very small compressions and expansions
involved in the transmission of sound. The divers must work together in
phase so that they do not cause 'hydraulic interference'.

Drawings and calculations elucidating the operation of the sodium
ATPsynthase/ATPase of the bacterium Propionigenium modestum have
recently been published (1). This is a rotary enzyme driven by an
electrochemical sodium gradient. The authors suggest that the same
mechanism operates in other ATPsynthase/ATPases, including the proton-
driven rotary enzyme of Escherischia coli. Much of the experimental
work in this field has been done on the rotary enzymes of bacteria, the
assumption being that they are similar to the rotary enzymes in the
mitochondria of eukaryotes. I make the same assumption here. (Rotary
ATPsynthase enzymes can be driven in reverse by the energy released
when ATP is split into ADP and inorganic phosphate. They then pump
sodium ions [or protons, as the case may be] against an electrochemical
gradient; in this mode of operation the appropriate name for them is

Other drawings (2) show the ATP-making (-cleaving) part of this class
of enzyme to consist of three compartments having what look to me
like 'double doors'; each pair of double doors opens and closes in
sequence, separated by 120 degrees of phase angle, as a central
asymmetric 'axle' is rotated by the passage of positive ions through
the 12-segmented rotor in the bacterial (or mitochondrial inner)
membrane. According to Boyer's binding exchange mechanism, each
catalytic site passes through a cycle of three different states: open,
loose and tight, corresponding to an empty state, a state with bound
ADP and phosphate, and a state with tightly bound ATP; at any given
moment the three sites are in a different state (3).

It is reasonable to assume that the ATPsynthase molecules of a
mitochondrion will rotate in synchrony because they are all identical
and are all driven by the same electrochemical gradient, which depends
on the concentrations of protons inside and outside the inner membrane.
These concentrations in turn depend on the activity of the other
respiratory enzymes in the mitochondrion.  I suggest that neighbouring
rotating ATPsynthases on the cristae of a mitochondrion will fall into
a phase relationship that minimises 'hydraulic interference' between
neighbours as their opposed 'double doors' open and shut. Thus all of
the identical rotary enzymes at the end of the respiratory chain will
rotate in phase at a frequency ultimately determined by the supply of
incoming metabolites and the metabolic activity of all of the 'earlier'
enzymes in the respiratory chain. I suggest that the full range of
frequencies of rotation of the ATPsynthase/ATPase might turn out to be
about 6 - 24 Hz.

The results of the calculations in (1) were that when the sodium-driven
rotary enzyme operated under a typical physiological electrochemical
gradient it rotated at about 15 - 20 Hz. It formed 3 molecules of ATP
per revolution. Twelve sodium ions passed through the rotary Fo part of
the enzyme (the 'motor') for each revolution, corresponding to an
average of 4 sodium ions per ATP molecule formed. The authors remarked
that the same operating principle could drive the proton-driven
ATPsynthases, with slight changes to the design of the Fo motor.

Other workers observing an isolated F1-ATPase unit by video microscopy
(4) have shown that it rotates in steps of 120 degrees.

I conclude from these papers that it is likely that the proton-driven
ATPsynthase enzymes in the cristae of mitochondria rotate at about 15 -
20 Hz (the precise rate depending on the electrochemical gradient
driving them). It is possible that when their movement is looked at in
fine detail they will be seen to advance in 12 small steps of 30
degrees per rotation (as shown in a figure of reference 1), at each
step releasing one proton at the bottom of the gradient. However, the
30-degree steps shown in (1) are derived from theoretical calculation;
they have not, as far as I am aware, been observed.

I assume that when the rotation of the ATPsynthase/ATPase enzyme is
looked at more broadly it is seen to advance in three big steps of 120
degrees per rotation (as observed in reference 4), at each big step
releasing one molecule of ATP and four protons at the bottom of the
gradient. I propose that all of these enzymes in a mitochondrion rotate
in phase, or in phase plus or minus 120 degrees; that is, they all take
a 120-degree step at precisely the same time.

The rate of the big steps will therefore be about 45 - 60 Hz. There is
an important coincidence here: this rate is about in the middle of
the 'gamma' range of oscillation (20 - 70 Hz) of certain neurons that
seem to play important roles in various forms of perception, awareness,
consciousness, and motor control. The precision of the timing of the
cycling of these oscillations has been observed to be about a
millisecond. Some workers have reported 'rhythmic' activity of neurons
oscillating at gamma frequencies; I assume that they mean regular
starting and stopping of the oscillations (5, 6, 7). As I suggested
above, the full range of frequencies of rotation might turn out to be
6 - 24 Hz (at least while the enzyme is operating as ATPase); this
would make the range of frequencies of the 'big steps' 18 - 72 Hz and
thus cover the full range of gamma oscillations.

If the same enzymes are driven in reverse, utilising the energy
released by the splitting of ATP, the same frequency relationships will
hold, I assume. The rotation rate will be about 15 - 20 Hz (perhaps 6 -
24 Hz). One ATP molecule will be split for each big step of 120 degrees
of rotation. Each enzyme will take 15 - 60 (perhaps 18 - 72) big steps
of rotation per second, precisely in phase with its neighbours, and in
each big step 4 protons will be pumped up the electrochemical gradient
to the outside of the inner membrane of the mitochondrion.

How might the (hypothetical) oscillations in a mitochondrion caused by
the ATPsynthase enzymes rotating synchronously in phase in the cristae
trigger oscillations of the same frequency in the 'firings' of a
neuron? One obvious possibility is that the mitochondrion will produce
minor 'floods' of ATP molecules at frequencies in the range of 45 - 60
Hz. The neuron uses ATP to drive the enzymes in its membrane that
repolarise the membrane after each 'firing'. If just enough ATP
molecules arrive at the membrane in minor 'floods' with a frequency of
(say) 45 Hz, the membrane could be repolarised at that frequency and so
could not fire at any higher frequency. However, it could fire at a
lower frequency. And in any case, because ATP is made inside the inner
membrane of the mitochondrion, and has to be carried outside by the
ATP/ADP translocators in that membrane, it is possible that an
oscillation in its supply inside the mitochondrion will be almost
completely 'smoothed out' or 'averaged' by the time the ATP arrives

Another possibility is that the ATPsynthase enzymes rotating in phase
will continually lower the concentration of protons outside the inner
membrane of the mitochondrion at a frequency in the range of 45 - 60
Hz. When operating as ATPsynthase they are driven by the
electrochemical gradient created by a high concentration of protons
outside the inner membrane and a low concentration of protons inside
it. (Other respiratory enzymes in the mitochondrion keep building up
the concentration of protons outside the inner membrane.) Inside the
membrane there may be a corresponding oscillating change in the
concentration of protons as protons are released in minor 'floods' from
the ATPsynthase enzymes.

If a sufficient number of excess protons passed through the outer
membrane of the mitochondrion (which has VDAC pores that make it freely
permeable to ions and most metabolites) (8) in minor 'floods' at
frequencies in the range of 45 - 60 Hz and reached a critical spot on
the membrane of the neuron they could depolarise the membrane at that
spot and so trigger impulses at the same frequency. (The membrane of a
neuron that is ready to fire is polarised by negative charges inside it
and positive charges outside it. Protons, which are positively charged,
arriving at the inner surface would depolarise the membrane and so
cause the neuron to fire.)

The question here is whether the ATPsynthase enzymes in a mitochondrion
inside a neuron would allow minor floods of excess protons to leave the
mitochondrion and cross a (small) gap to the inside of the membrane of
the neuron. ATPsynthase might pass protons so quickly from outside the
inner membrane of the mitochondrion to inside that no excess protons
could pass from the mitochondrion to the membrane of the neuron. And it
is possible that the positive charge of the protons outside the inner
membrane of the mitochondrion is balanced, partly or wholly, by the
negative charge of anions inside the inner membrane, so that the
protons on the outside are 'tied' by the attractive force between them
and the anions. (That is to say, the inner membrane of the
mitochondrion might be partly or completely polarised when
ATPsynthase/ATPase is working as the synthase. I have no information on

Because of the doubts outlined above I think it likely that, if
mitochondria are indeed the motors of consciousness, they trigger the
rhythmic firings of certain neurons at the gamma frequencies only when
the rotary enzymes are working as ATPases, fuelled by ATP and pumping
protons from inside the inner membrane of the mitochondrion to outside
it. I propose that when working thus they can produce minor 'floods' of
excess protons that can quickly cross a small gap from the
mitochondrion to the inside of the membrane of a neuron. The 'floods'
of protons arrive at a gamma frequency and trigger firings of the
neuron at the same gamma frequency. When the mitochondrion exhausts (or
nearly exhausts) the supply of ATP inside it the ATPase has to stop
using ATP as a fuel; it then rotates in the reverse direction and is
driven as ATPsynthase by the flow of protons from outside the inner
membrane to inside.

Thus the neuron will be triggered at a gamma frequency until the
mitochondrion runs out of ATP. Then the triggering will stop for a
while, while the mitochondrion 'recharges' its supply of ATP. This
explains the rhythmic pattern observed in the gamma oscillations.

If mitochondria are the motors of consciousness because they can drive
certain neurons each at a single gamma frequency characteristic of that
neuron at any one time (or of a group of neurons of which it is a
member) it is possible that there has been natural selection for a
lower mitochondrial mutation rate in humans than in other animals. This
is so because higher consciousness (especially the ability to use
language) gives humans many advantages in the struggle to survive and

Mutations (either maternally inherited or somatic) in mitochondrial DNA
could produce populations of mitochondria that oscillated at different
frequencies in certain single neurons important in the creation of an
aspect of the conscious state. The driving of a single neuron at two or
more different gamma frequencies would presumably destroy the aspect of
consciousness that its firing would normally help to create.

(Note. I suggest that rotary enzymes might play important roles in the
simple information systems of bacteria and single-celled eukaryotes.
The slime mould that extends itself through the shortest path in a
maze, for example, might depend on a sonar system driven by the
oscillations of mitochondria.)


1) Dimroth P et al (1999), Proceedings National Academy of Sciences 96
(9): 4924-4929.

2) Scientific American, January 1998, p 9.

3) Saraste M (review) (1999) Science 283:1488-1493.

4) Noji H (essay with drawing) (1998) Science 282:1844, 1845.

5) Maldonado P E et al (2000) Cereb Cortex 10(11): 1117-1131.

6) Palva  J M et al (2000) J Neurosci 20(3): 1170-1178.

7) Mima T et al (1999) Neurosci Lett 275(2): 77-80.

8) Green D R et al (1998) Science 281:1309-1312.

Andrew Gyles


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