Cardiolipin (IUPAC name 1,3-bis(sn-3’-

phosphatidyl)-sn-glycerol) is an important

component of the inner mitochondrial

membrane, where it constitutes about 20%

of the total lipid composition. It can also be

found in the membranes of most bacteria.

The name "cardiolipin" is derived from the

fact that it was first found in animal hearts. It

was first isolated from beef heart in the early

1940s.[1] In mammalian cells, but also in

plant cells,[2][3] cardiolipin (CL) is found

almost exclusively in the inner mitochondrial

membrane, where it is essential for the

optimal function of numerous enzymes that

are involved in mitochondrial energy

mCardiolipin (CL) is a kind of

diphosphatidylglycerol lipid. Two

phosphatidic acid moieties connect with a

glycerol backbone in the center to form a

dimeric structure. So it has four alkyl groups

and potentially carries two negative charges.

As there are four distinct alkyl chains in

cardiolipin, the potential for complexity of

this molecule species is enormous. However,

in most animal tissues, cardiolipin contains

18-carbon fatty alkyl chains with 2

unsaturated bonds on each of them.[4] It has

been proposed that the (18:2)4 acyl chain

configuration is an important structural

requirement for the high affinity of CL to

inner membrane proteins in mammalian

mitochondria.[5] However, studies with

isolated enzyme preparations indicate that

its importance may vary depending on the

protein examined.Since there are two

phosphates in the molecule, each of them

can catch one proton. Although it has a

symmetric structure, ionizing one phosphate

happens at a very different levels of acidity

than ionizing both: pK1 = 3 and pK2 > 7.5. So

under normal physiological conditions

(wherein pH is around 7), the molecule may

carry only one negative charge. The hydroxyl

groups (–OH and –O−) on phosphate would

form a stable intramolecular hydrogen bond

with the centered glycerol's hydroxyl group,

thus forming a bicyclic resonance structure.

This structure traps one proton, which is

quite helpful for oxidative

phosphorylation.As the head group forms

such compact.bicycle structure, the head

group area is quite small relative to the big

tail region consisting of 4 acyl chains. Based

on this special structure, the fluorescent

mitochondrial indicator, nonyl acridine

orange (NAO) was introduced in 1982,[6] and

was later found to target mitochondria by

binding to CL. NAO has a very large head and

small tail structure which can compensate

with cardiolipin's small head large tail

structure, and arrange in a highly ordered

way.[7] Several studies were published

utilizing NAO both as a quantitative

mitochondrial indicator and an indicator of

CL content in mitochondria. However, NAO is

influenced by membrane potential and/or

the spatial arrangement of CL,[8][9][10] so

it's not proper to use NAO for CL or

mitochondria quantitative studies of intact

respiring mitochondria. But NAO still

represents a simple method of assessing CL

content.etabolism.