This week–

YOU stick an address on a letter to

tell it where to go – so why not do

the same for proteins? A clever bit

of “molecular addressing” might

correct mitochondrial diseases,

and perhaps even delay ageing.

Mitochondria are often

referred to as the power plants

of the cell because they perform

most of the chemical reactions

that transform sugars into usable

energy. However, mutations in

the genes that control this process

are common. Mitochondrial

diseases affect at least 1 in 5000

people and can lead to a variety

of serious, incurable metabolic

diseases , including disorders

of the nervous system and

blindness. The gradual

accumulation of mutations in

mitochondria over a lifetime

could also be an important cause

of ageing .

Many of the genes responsible

for energy production are made

up of mitochondrial DNA, rather

than DNA in the cell’s nucleus –

and an obvious solution to

mitochondrial errors would

be to introduce a normal copy

of the defective gene into the

mitochondrial DNA. However, so

far researchers have been unable

to transport genes across the

mitochondrial membrane into

the mitochondria themselves. If

they insert the gene elsewhere in

the cell, the protein it codes for

will often fail to fold correctly and

thus cannot do its job.

To solve this problem, Marisol

Corral-Debrinski and her

colleagues at the Pierre and Marie

Curie University in Paris, France,

picked two mitochondrial gene

mutations: one that causes a

syndrome characterised by

muscle weakness, lack of co-

ordination and retinal problems,

and another which is responsible

for a form of blindness called

Leber hereditary optic

neuropathy (LHON).

The team then tagged normal

versions of these genes with two

separate cellular “address codes”

and inserted them into the

cytoplasm of cells grown in a lab

dish. The first code directs the

messenger RNA – the molecule

that carries the instructions for

making a protein – to the surface

of the mitochondria, ensuring

that the protein gets made at the

mitochondrial membrane. The

second address code, known as

the mitochondrial targeting

sequence, tells the protein to

enter the mitochondria.

Researchers have previously tried

using one or the other of these

tags, but not both. “To get the best

result, you need both of them

combined,” says Corral-Debrinski.

Sure enough, these double-

tagged genes were able to

completely reverse the effect of

both mitochondrial mutations in

the cell cultures for up to a year

(Rejuvenation Research, DOI:

10.1089/rej.2006.0526).

“It’s a really smart idea,” says

Eric Schon, a mitochondrial

researcher at Columbia University

in New York. However, he adds,

“it’s [only] the next step in the

long, hard slog to getting this to

work perfectly”.

Corral-Debrinski is now

planning to test the gene

therapy on lab rats.

As ever with gene therapy,

before the technique can be

transformed into a useful human

treatment, researchers will have

to find a way to get the normal

genes to the right parts of the

body safely without causing

harmful side effects on other

tissues.

However, LHON may be easier

to treat with gene therapy than

most diseases, says Corral-

Debrinski, because the eye is well

isolated. This means that you can

inject small quantities of the gene

construct into the eye, and it

won’t become distributed all over

the body, she says.

If all the problems can be

solved, double-tagging genes may

also provide a way of introducing

other proteins into mitochondria

to stop some of the effects of

ageing. For example, researchers

might like to insert antioxidant

enzymes to see if reducing

oxidative damage to

mitochondrial DNA will lead to

fewer mutations, which could in

turn delay ageing, Schon says. ●

Correct address may fix faulty genes

“Double-tagged genes were able

to reverse the effect of both

mitochondrial mutations in cell

cultures for up to a year”

BOB HOLMES

14 | NewScientist | 18 August 2007 www.newscientist.com

THIS WEEK 50 YEARS AGO Stars of radioLast week Britain’s greatest scientifi c

instrument, the 250-foot radio telescope

at Jodrell Bank in Cheshire, began

experimental work, and astronomers

are fi nding that its performance exceeds

their highest expectations. Much credit

is due to Professor Bernard Lovell, who

planned the project when radio

astronomy was still in its infancy.

However regrettable it may be that

the telescope cost more than was

expected, fi nancial controversy must

not be allowed to detract from the

brilliance of the project. Britain now

leads the world in this most recent

branch of astronomy, but the

government must be prepared to

spend even more, because after

obtaining a telescope that is the envy

of the world, the nation would be

open to ridicule if its programme were

impeded by a lack of funds. Radio

astronomy has replaced nuclear physics

as the chief intellectual sounding

board. Who can set a limit on its value?

Selling like frozen cakesTraditionally bakers work by night, since

the public demands that its bread is

absolutely fresh when bought from

the shop. However, increasing wage

bills mean it is becoming ever more

expensive to bake bread overnight.

With this in mind, over the past few

years larger bakeries have become

interested in the possibility of storing

bread and other baked foods by deep-

freezing. Some are already selling

bread from the freezer. Bread kept in

this way remains fresh for quite a long

time, and some experiments show it

can remain so in a deep freeze for as

long as 12 weeks. The mechanisms are

not yet fully understood, although it is

believed that freezing the bread stops

water evaporating from it and hinders

chemical changes that normally take

place in the starch.

Whatever the reason, it looks like

frozen bread and frozen cakes will one

day be widely on sale in our shops.

From The New Scientist, 22 August 1957

MITOCHONDRIAL FIX

Adding an “address code” sends mRNA from normal genes to the mitochondria, where they can

be translated into protein

Normal version of gene

inserted into DNA with 2

mitochondrial address codes

Normal gene

Messenger RNA

Normal

protein

NUCLEUS

DNA

RIBOSOME

MITOCHONDRION

These address codes direct the mRNA

message to the mitochondria, where a

ribosome translates it into protein and

shuttles it inside to correct the deficiency

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