How many parents does it take to change a lipid?  In some cases, it takes “three parents”.  Recent news in the British media has highlighted a debate about ethics in assisted conception.  The Human Fertilisation and Embryology Authority (HFEA) has initiated a consultation about the public response to what has been dubbed “3 parent IVF”.  This debate has been regarded as moot by informed scientists, as the “third parent” in this case provides no human DNA at all, but is a supply of healthy symbiotic organelles called mitochondria.  This procedure is thus equivalent to organ replacement, though it takes place at cellular level. This sort of intervention is well known as a serious undertaking, and begs the question of what sort of problems could require such an intervention. A surprising number are lipid-based.

The lipid basis for mitochondrial disease has far-reaching physical and metabolomic consequences as, unlike most organelles, the correct chemical activity of a mitochondrion relies upon not one but two plasma-type membranes. When we also consider that mitochondria are the organelles that all terrestrial organisms rely upon for releasing chemical energy from glucose, their function is clearly of paramount importance. Thus a fault with one or both of these membranes in the handful of mitochondria in the ovum at conception may give rise to profound effects in the resulting individual.

One such condition is called Barth Syndrome [1]. In this condition it appears that both the fatty acid composition and the amount of cardiolipin are abnormal in the inner mitochondrial membrane. This can deform and even destroy the bi-layer, rendering the mitochondrion useless for its normal function. In practice, this means that muscular function is compromised, especially in cardiac tissue. There are also a number of immunological effects surrounding a low bodily population of neutrophils – the cells used for managing infection. The severity of the symptoms has led to the formation of a number of support groups, such as the Barth Syndrome Foundation*.

Barth syndrome is an X chromosome disorder and is thus more common in males than females, as males possess only one X chromosome. In order for a female to display the condition, her mother would have to be a carrier or display the condition, and her father would also have to display the condition. A mutation of the X chromosome leading to the condition is observable on a molecular level by abnormalities in tafazzin. Tafazzin is an enzyme called an acyltransferase, meaning it is capable of transferring a fatty acid residue from one hydroxyl group to another, including between two individual lipid species. Recent work by Schlame et al. [2], suggests that this enzyme lacks specificity of lipid substrate, but is influenced by the topology of the membrane. This may limit its activity to only very small portions of the membrane (perhaps less than 1%), though in systems where tafazzin is defective, the small areas in which the topology is undesirable for the organelle (and thus the cell) are not corrected. On a general (clinical) level, this means that chemical energy (glucose) is not converted to mechanical energy efficiently. Under normal circumstances, tafazzin helps manage the inner mitochondrial membrane in order that it maintains the correct topology and permeability.

There is also evidence that better-known conditions such as Myalgic Encephalitis (M.E., also known as chronic fatigue syndrome) and type II diabetes may be either directed or mediated by lipid damage or abnormality in mitochondria. Nicholson and Ellithorpe have presented evidence that the dietary application of fresh lipids and anti-oxidants to human patients with Myalgic Encephalitis reduces their symptoms; however it is not clear how these clinical trials were conducted. Perhaps more reliably, a comprehensive body of research now suggests that mitochondrial dysfunction is a factor in the insulin resistance that defines type II diabetes [3]. Notably type II diabetes is associated with older people, and so it is not until other factors that weaken mitochondrial function have had time to take hold, that symptoms associated with insulin resistance are observed. Thus, the occurrence of such conditions in the offspring of child-bearing age adults is not predictable without a comprehensive medical history. The direct female line of the potential offspring is especially important in this as this is the source of the mitochondria.

The fact that mitochondrial disease can be the result of both genetic and dietary problems should alert us to the global significance of this set of conditions. Undoubtedly a variety of approaches is needed to manage the problems involved, but we should be aware that individuals affected by such conditions may be preyed on for the sale of quack ‘cures’, if there are not readily-available and effective treatments that have been soundly tested in a clinical setting.


*This page is not intended as a scientific reference but for public/charitable bodies relevant to this condition.


[1] P.G. Barth, H.R. Scholte, J.A. Berden, J.M. Van Der Klei-Van Moorsel, I.E.M. Luyt-Houwen, E.Th. Van’T Veer-Korthof, J.J. Van Der Harten, M.A. Sobotka-Plojhar, Journal of the Neurological Sciences, 1983, 62, 327-355.

[2] M. Schlame, D. Acehan, B. Berno, Y. Xu, S. Valvo, M. Ren, D. L. Stokes, R. M. Epand, Nature Chemical Biology, 2012, 8, 862–869.

[3] J. Kim, Y. Wei and J. R. Sowers, Circulation Research, 2008, 102, 401-414.