Nucleoid associated proteins and their function
Human mitochondrial DNA (mtDNA), ‘our other genome’, was fully sequenced in 1981 and represents a separate genome present from several hundreds to thousands of copies per cell. It encodes thirteen protein subunits of the respiratory chain and ATP synthase, plus the 2 rRNAs and 22 tRNAs required for their synthesis on mitochondrial ribosomes (See the figure below). The 13 mtDNA encoded proteins are subunits of four of the five oxidative phosphorylation complexes and therefore indispensible for cellular energy production. Maintenance of an intact mitochondrial genome is therefore essential for viability and for the completion of development. In mammals, mtDNA is exclusively inherited via the maternal line, thus mtDNA disease mutations are solely transmitted from mother to offspring. MtDNA disease mutations can be classified as maternally inherited or ‘spontaneous’ germline mutations, but can also be the consequence of mutations in nuclear genes coding for proteins involved in mtDNA maintenance. In the latter case, the disease is often restricted to some tissues and does not normally affect the female germline. Inheritance is thus Mendelian and most nuclear ‘mtDNA disease’ genes have been identified using the rationale of Mendelian disease genetics.
Gerhold JM, Cansiz-Arda Ş, Lõhmus M, Engberg O, Reyes A, van Rennes H, Sanz A, Holt IJ, Cooper HM, Spelbrink JN (2015) Human Mitochondrial DNA-Protein Complexes Attach to a Cholesterol-Rich Membrane Structure. Sci Rep, 5:15292.
Fernández-Millán P, Lázaro M, Cansız-Arda Ş, Gerhold JM, Rajala N, Schmitz CA, Silva-Espiña C, Gil D, Bernadó P, Valle M, Spelbrink JN, Solà M (2015) The hexameric structure of the human mitochondrial replicative helicase Twinkle. Nucleic Acids Res, 43:4284-4295.
Rajala N, Gerhold JM, Martinsson P, Klymov A, Spelbrink JN (2014) Replication factors transiently associate with mtDNA at the mitochondrial inner membrane to facilitate replication. Nucleic Acids Res, 42:952-967
Radboud Center for Mitochondrial Medicine, Radboud University Medical Centre
Geert Grooteplein 10
NL-6500 HB Nijmegen, The Netherlands