You can search (by keyword) in KEGG Disease(http://www.genome.jp/kegg/disease/), OR Disease Database(http://www.diseasesdatabase.com/begin.asp)......

In Mitomap database (http://www.mitomap.org) follow to the links at: "mtDNA Mutations with Reports of Disease-Associations" section:

http://www.mitomap.org/bin/view.pl/MITOMAP/MutationsRNA

http://www.mitomap.org/bin/view.pl/MITOMAP/MutationsCodingControl

click on the particular disease to go to the list of diseases

http://www.mitomap.org/bin/view.pl/MITOMAP/DiseaseList

For disease description, you can search the OMIM database at NCBI:

http://www.ncbi.nlm.nih.gov/omim

In adittion I would suggest

http://www.mitomap.org/MITOMAP

http://www.mtdb.igp.uu.se/

http://bioinfo.nist.gov/

http://www.hmtdb.uniba.it:8080/hmdb/

http://empop.org/

http://www.smgf.org/pages/mtdatabase.jspx

http://www.mitoproteome.org/

Hope that they'll be useful

Happy Easter!

Manuel

Disruption of ATP-binding cassette B8 in mice leads to cardiomyopathy through a decrease in mitochondrial iron export

Yoshihiko Ichikawa1, Marina Bayeva1, Mohsen Ghanefar, Vishnu Potini, Lin Sun, R. Kannan Mutharasan, Rongxue Wu, Arineh Khechaduri, Tejaswitha Jairaj Naik, and Hossein Ardehali2

+ Author Affiliations

Feinberg Cardiovascular Research Institute, Northwestern University School of Medicine, Chicago, IL 60611

Edited* by Christine E. Seidman, Harvard Medical School, Boston, MA, and approved January 23, 2012 (received for review November 23, 2011)

Abstract

Mitochondrial iron levels are tightly regulated, as iron is essential for the synthesis of Fe/S clusters and heme in the mitochondria, but high levels can cause oxidative stress. The ATP-binding cassette (ABC) transporter ABCB8 is a mitochondrial inner membrane protein with an unknown function. Here, we show that ABCB8 is involved in mitochondrial iron export and is essential for baseline cardiac function. Induced genetic deletion of ABCB8 in mouse hearts resulted in mitochondrial iron accumulation and cardiomyopathy, as assessed by echocardiography and invasive hemodynamics. Mice with ABCB8 deletion in the heart also displayed mitochondrial damage, and higher levels of reactive oxygen species and cell death. Down-regulation of ABCB8 in vitro resulted in decreased iron export from isolated mitochondria, whereas its overexpression had the opposite effect. Furthermore, ABCB8 is needed for the maturation of the cytosolic Fe/S proteins, as its deletion in vitro and in vivo led to decreased activity of cytosolic, but not mitochondrial, iron–sulfur-containing enzymes. These results indicate that ABCB8 is essential for normal cardiac function, maintenance of mitochondrial iron homeostasis and maturation of cytosolic Fe/S proteins. In summary, this report provides characterization of a protein involved in mitochondrial iron export.

Footnotes

↵1Y.I. and M.B. contributed equally to this work.

↵2To whom correspondence should be addressed. E-mail: [email protected].

Author contributions: Y.I., M.B., M.G., R.K.M., and H.A. designed research; Y.I., M.B., M.G., V.P., L.S., R.W., A.K., T.J.N., and H.A. performed research; Y.I., M.B., M.G., and H.A. analyzed data; and M.B. and H.A. wrote the paper.

The authors declare no conflict of interest.

↵*This Direct Submission article had a prearranged editor.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1119338109/-/DCSupplemental.

Posted: Saturday, April 07, 2012 6:26:26 PM

Rank: Advanced Member

Groups: Member

Joined: 2/15/2009

Posts: 2,722

Dichloroacetic acid (DCA) in cancer is analogous to OSC in ALS; a non-patentable simple molecule that patients started to take since they didn't have time to wait for FDA.

PLoS ONE 7(4):2012

Modulation of Astrocytic Mitochondrial Function by Dichloroacetate Improves Survival and Motor Performance in Inherited Amyotrophic Lateral Sclerosis

Miquel E , Cassina A , Martínez-Palma L , Bolatto C , Trías E , et al.

Abstract

Mitochondrial dysfunction is one of the pathogenic mechanisms that lead to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). Astrocytes expressing the ALS-linked SOD1G93A mutation display a decreased mitochondrial respiratory capacity associated to phenotypic changes that cause them to induce motor neuron death. Astrocyte-mediated toxicity can be prevented by mitochondria-targeted antioxidants, indicating a critical role of mitochondria in the neurotoxic phenotype. However, it is presently unknown whether drugs currently used to stimulate mitochondrial metabolism can also modulate ALS progression. Here, we tested the disease-modifying effect of dichloroacetate (DCA), an orphan drug that improves the functional status of mitochondria through the stimulation of the pyruvate dehydrogenase complex activity (PDH). Applied to astrocyte cultures isolated from rats expressing the SOD1G93A mutation, DCA reduced phosphorylation of PDH and improved mitochondrial coupling as expressed by the respiratory control ratio (RCR). Notably, DCA completely prevented the toxicity of SOD1G93A astrocytes to motor neurons in coculture conditions. Chronic administration of DCA (500 mg/L) in the drinking water of mice expressing the SOD1G93A mutation increased survival by 2 weeks compared to untreated mice. Systemic DCA also normalized the reduced RCR value measured in lumbar spinal cord tissue of diseased SOD1G93A mice. A remarkable effect of DCA was the improvement of grip strength performance at the end stage of the disease, which correlated with a recovery of the neuromuscular junction area in extensor digitorum longus muscles. Systemic DCA also decreased astrocyte reactivity and prevented motor neuron loss in SOD1G93A mice. Taken together, our results indicate that improvement of the mitochondrial redox status by DCA leads to a disease-modifying effect, further supporting the therapeutic potential of mitochondria-targeted drugs in ALS.

Full Text

The clinical effect of DCA is targeting astrocytes while having a limited effect on motor neurons and it seems well worth to evaluate a bit more in detail.

Meanwhile, see e.g. this paper and websites cited therein.

Mark

Thanx 2 all....

Mark

try KEGG pathway search for mitochondrial proteins. u can use uniprot search too, customizee results to show KEGG in crossreference

One more uneful link http://www.genome.jp/kegg/disease/

Thanx Saurabh....

Your question may be too general,and although data Bases exist,more relevant information may be garnered by asking a more specific Question,ie; "Mitochondrial iron levels are tightly regulated, as iron is essential for the synthesis of Fe/S clusters and heme in the mitochondria, but high levels can cause oxidative stress. "?

You can go to the home page of the NCBI, and search for mitochondrial diseases in humans.

Hi Lee!

I am Working on the comparative analysis of the Human associated mt diseases and the closely related organisms like mouse, chimpanzee. I want to study the difference in the genes of the associated diseases.

Thanx for your support.