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Review
, 139 (3), 381-399

Mitonuclear Genomics and Aging

Affiliations
Review

Mitonuclear Genomics and Aging

Joseph C Reynolds et al. Hum Genet.

Abstract

Our cells operate based on two distinct genomes that are enclosed in the nucleus and mitochondria. The mitochondrial genome presumably originates from endosymbiotic bacteria. With time, a large portion of the original genes in the bacterial genome is considered to have been lost or transferred to the nuclear genome, leaving a reduced 16.5 Kb circular mitochondrial DNA (mtDNA). Traditionally only 37 genes, including 13 proteins, were thought to be encoded within mtDNA, its genetic repertoire is expanding with the identification of mitochondrial-derived peptides (MDPs). The biology of aging has been largely unveiled to be regulated by genes that are encoded in the nuclear genome, whereas the mitochondrial genome remained more cryptic. However, recent studies position mitochondria and mtDNA as an important counterpart to the nuclear genome, whereby the two organelles constantly regulate each other. Thus, the genomic network that regulates lifespan and/or healthspan is likely constituted by two unique, yet co-evolved, genomes. Here, we will discuss aspects of mitochondrial biology, especially mitochondrial communication that may add substantial momentum to aging research by accounting for both mitonuclear genomes to more comprehensively and inclusively map the genetic and molecular networks that govern aging and age-related diseases.

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References

    1. Nat Chem Biol. 2015 Dec;11(12):909-16 - PubMed

References

    1. Cold Spring Harb Perspect Biol. 2013 May 01;5(5):a011080 - PubMed

References

    1. Proteomics. 2018 May;18(10):e1700035 - PubMed

References

    1. Curr Opin Cell Biol. 2015 Apr;33:125-31 - PubMed

References

    1. Science. 2017 Apr 21;356(6335):323-327 - PubMed

References

    1. Science. 2014 Nov 7;346(6210):748-51 - PubMed

References

    1. Nat Rev Mol Cell Biol. 2016 Apr;17(4):213-26 - PubMed

References

    1. Annu Rev Biochem. 2011;80:1033-53 - PubMed

References

    1. J Gerontol. 1956 Jul;11(3):298-300 - PubMed

References

    1. Synapse. 2010 Jan;64(1):83-91 - PubMed

References

    1. EMBO J. 2014 May 2;33(9):981-93 - PubMed

References

    1. Biogerontology. 2009 Dec;10(6):773-81 - PubMed

References

    1. Gene. 2002 Mar 6;286(1):127-34 - PubMed

References

    1. Biochem Biophys Res Commun. 2001 May 4;283(2):460-8 - PubMed

References

    1. J Neurosci Res. 2005 Mar 1;79(5):714-23 - PubMed

References

    1. Trends Cell Biol. 2017 Sep;27(9):685-696 - PubMed

References

    1. Int J Mol Sci. 2015 Feb 27;16(3):4518-59 - PubMed

References

    1. NPJ Aging Mech Dis. 2016 Aug 18;2:16017 - PubMed

References

    1. Pediatr Diabetes. 2018 Apr 25;: - PubMed

References

    1. J Cell Physiol. 2019 May;234(5):6601-6610 - PubMed

References

    1. Nature. 1981 Apr 9;290(5806):470-4 - PubMed

References

    1. Cell. 2013 Jun 6;153(6):1194-217 - PubMed

References

    1. Cell Metab. 2015 Mar 3;21(3):443-54 - PubMed

References

    1. Epigenomics. 2012 Feb;4(1):17-27 - PubMed

References

    1. J Biol Chem. 2014 Apr 18;289(16):10950-7 - PubMed

References

    1. Cell Res. 2018 Mar;28(3):281-295 - PubMed

References

    1. J Theor Biol. 2017 Dec 7;434:58-67 - PubMed

References

    1. Eur J Immunol. 2014 May;44(5):1552-62 - PubMed

References

    1. Mitochondrion. 2019 May;46:22-29 - PubMed

References

    1. Nat Med. 2008 Sep;14(9):949-53 - PubMed

References

    1. Int J Mol Sci. 2019 May 17;20(10): - PubMed

References

    1. Genes Brain Behav. 2006;5 Suppl 2:92-107 - PubMed

References

    1. Aging Cell. 2015 Dec;14(6):921-3 - PubMed

References

    1. Physiol Rep. 2019 Jul;7(13):e14171 - PubMed

References

    1. Biochem Biophys Res Commun. 2013 Oct 18;440(2):197-203 - PubMed

References

    1. Ageing Res Rev. 2017 Jan;33:89-104 - PubMed

References

    1. Nucleic Acids Res. 1990 Dec 11;18(23):6927-33 - PubMed

References

    1. Dev Cell. 2012 Mar 13;22(3):660-8 - PubMed

References

    1. Nature. 1981 Apr 9;290(5806):457-65 - PubMed

References

    1. J Appl Physiol (1985). 2014 Oct 15;117(8):869-79 - PubMed

References

    1. Mitochondrion. 2018 Jan;38:31-40 - PubMed

References

    1. Mol Cell Biochem. 2003 Dec;254(1-2):83-9 - PubMed

References

    1. Curr Genet. 2018 Feb;64(1):199-214 - PubMed

References

    1. PLoS One. 2009 Jul 22;4(7):e6334 - PubMed

References

    1. Nat Cell Biol. 2007 Jun;9(6):660-5 - PubMed

References

    1. Hum Mol Genet. 2004 Dec 15;13(24):3219-27 - PubMed

References

    1. Elife. 2016 Nov 17;5: - PubMed

References

    1. Oncotarget. 2017 Aug 10;8(55):94900-94909 - PubMed

References

    1. Science. 2013 Sep 20;341(6152):1345-6 - PubMed

References

    1. Mol Cell. 2018 Mar 1;69(5):757-772.e7 - PubMed

References

    1. Sci Rep. 2017 Aug 10;7(1):7802 - PubMed

References

    1. Nat Rev Mol Cell Biol. 2015 Oct;16(10):593-610 - PubMed

References

    1. PLoS Genet. 2014 May 15;10(5):e1004354 - PubMed

References

    1. Mol Cell. 2012 Apr 13;46(1):91-104 - PubMed

References

    1. Cell Metab. 2015 Aug 4;22(2):204-6 - PubMed

References

    1. Biochem Biophys Res Commun. 2016 Aug 5;476(4):412-419 - PubMed

References

    1. Genetics. 2003 Jan;163(1):35-46 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9186-91 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2019 Aug 6;116(32):16028-16035 - PubMed

References

    1. BMC Genomics. 2019 Sep 2;20(1):691 - PubMed

References

    1. Mol Cell Biol. 2004 Nov;24(22):9823-34 - PubMed

References

    1. Genes (Basel). 2018 Jan 09;9(1): - PubMed

References

    1. J Alzheimers Dis. 2006 Jul;9(2):183-93 - PubMed

References

    1. Mol Metab. 2016 Oct 31;6(1):125-137 - PubMed

References

    1. Cell Metab. 2016 Dec 13;24(6):795-806 - PubMed

References

    1. J Mol Med (Berl). 2019 Apr;97(4):473-485 - PubMed

References

    1. Peptides. 2009 Jun;30(6):1197-202 - PubMed

References

    1. Hum Genet. 2003 Mar;112(3):303-9 - PubMed

References

    1. J Biol Chem. 1996 May 24;271(21):12275-80 - PubMed

References

    1. Front Endocrinol (Lausanne). 2019 May 31;10:331 - PubMed

References

    1. Circulation. 1998 Jun 2;97(21):2099-100 - PubMed

References

    1. Plant Physiol. 2005 Jul;138(3):1723-33 - PubMed

References

    1. Nature. 2009 Apr 23;458(7241):1056-60 - PubMed

References

    1. Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-9 - PubMed

References

    1. Science. 2019 Nov 15;366(6467):827-832 - PubMed

References

    1. Aging (Albany NY). 2016 Jan;8(1):50-61 - PubMed

References

    1. Science. 1999 Mar 5;283(5407):1482-8 - PubMed

References

    1. Cells. 2018 Aug 13;7(8): - PubMed

References

    1. Nature. 2013 May 23;497(7450):451-7 - PubMed

References

    1. Cell Metab. 2019 Jan 8;29(1):78-90.e5 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):1821-1822 - PubMed

References

    1. EBioMedicine. 2018 Oct;36:316-328 - PubMed

References

    1. Genome Biol Evol. 2019 Jul 1;11(7):1883-1896 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6136-41 - PubMed

References

    1. Pharmacol Res. 2019 Sep;147:104381 - PubMed

References

    1. Nat Rev Genet. 2004 Feb;5(2):123-35 - PubMed

References

    1. Heredity (Edinb). 2016 Mar;116(3):338-47 - PubMed

References

    1. Cell. 2019 Mar 21;177(1):200-220 - PubMed

References

    1. J Biol Chem. 2008 Dec 19;283(51):35724-34 - PubMed

References

    1. Nucleic Acids Res. 1996 Feb 15;24(4):648-54 - PubMed

References

    1. Biochem J. 2013 Oct 15;455(2):157-67 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13042-7 - PubMed

References

    1. Trends Genet. 2019 Mar;35(3):186-198 - PubMed

References

    1. Science. 2011 Jan 28;331(6016):456-61 - PubMed

References

    1. Biol Rev Camb Philos Soc. 2019 Jun;94(3):1089-1104 - PubMed

References

    1. Nat Genet. 2008 Apr;40(4):392-4 - PubMed

References

    1. Int J Cardiol. 2018 Mar 1;254:23-27 - PubMed

References

    1. J Physiol. 2016 Sep 15;594(18):5135-47 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2019 Aug 6;116(32):15763-15765 - PubMed

References

    1. Nat Rev Genet. 2014 Mar;15(3):193-204 - PubMed

References

    1. Elife. 2015 Dec 19;4:e08890 - PubMed

References

    1. Front Genet. 2017 Mar 03;8:25 - PubMed

References

    1. Free Radic Biol Med. 2011 Jul 15;51(2):327-36 - PubMed

References

    1. Annu Rev Biochem. 2007;76:679-99 - PubMed

References

    1. Cell. 1987 Oct 9;51(1):89-99 - PubMed

References

    1. J Transl Med. 2019 May 14;17(1):157 - PubMed

References

    1. Aging Cell. 2015 Aug;14(4):497-510 - PubMed

References

    1. Mol Cell. 2016 Mar 3;61(5):654-666 - PubMed

References

    1. J Evol Biol. 2016 Apr;29(4):736-47 - PubMed

References

    1. Trends Endocrinol Metab. 2013 May;24(5):222-8 - PubMed

References

    1. Nature. 2015 May 14;521(7551):173-179 - PubMed

References

    1. Redox Biol. 2017 Apr;11:30-37 - PubMed

References

    1. Dose Response. 2014 Jan 31;12(2):288-341 - PubMed

References

    1. Nat Rev Endocrinol. 2016 Jan;12(1):43-60 - PubMed

References

    1. Cell Metab. 2017 Apr 4;25(4):765-776 - PubMed

References

    1. Bioessays. 2018 Sep;40(9):e1800102 - PubMed

References

    1. Nature. 2018 Dec;564(7736):434-438 - PubMed

References

    1. Science. 2000 Sep 1;289(5484):1567-9 - PubMed

References

    1. Cell. 2014 Jul 3;158(1):84-97 - PubMed

References

    1. Invest Ophthalmol Vis Sci. 2016 Mar;57(3):1238-53 - PubMed

References

    1. Mol Immunol. 2017 Dec;92:151-160 - PubMed

References

    1. Trends Genet. 2006 Feb;22(2):90-5 - PubMed

References

    1. Hum Mutat. 2009 Feb;30(2):E386-94 - PubMed

References

    1. J Mol Evol. 1994 Aug;39(2):174-90 - PubMed

References

    1. Mitochondrion. 2019 Nov;49:12-18 - PubMed

References

    1. Genome Med. 2017 Mar 29;9(1):31 - PubMed

References

    1. Mol Cell. 2012 Oct 26;48(2):158-67 - PubMed

References

    1. Semin Cancer Biol. 2017 Dec;47:101-109 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):E478-E487 - PubMed

References

    1. Cell Metab. 2007 Oct;6(4):280-93 - PubMed

References

    1. Am J Physiol Heart Circ Physiol. 2018 Nov 1;315(5):H1127-H1136 - PubMed

References

    1. Biochem J. 2014 Jul 15;461(2):223-32 - PubMed

References

    1. Front Biosci (Landmark Ed). 2017 Jan 1;22:835-853 - PubMed

References

    1. Science. 2003 Feb 28;299(5611):1346-51 - PubMed

References

    1. Mol Biol Cell. 2007 Sep;18(9):3225-36 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6336-41 - PubMed

References

    1. Mech Ageing Dev. 2016 Mar;154:1-8 - PubMed

References

    1. Biochem J. 2009 Jan 1;417(1):1-13 - PubMed

References

    1. Annu Rev Genet. 2017 Nov 27;51:1-22 - PubMed

References

    1. Cell Rep. 2014 Sep 11;8(5):1365-79 - PubMed

References

    1. Bioessays. 2011 Nov;33(11):860-9 - PubMed

References

    1. Cell. 2016 May 19;165(5):1197-1208 - PubMed

References

    1. Nature. 2016 May 11;533(7604):499-503 - PubMed

References

    1. J Inherit Metab Dis. 2019 Jan;42(1):3-4 - PubMed

References

    1. Nat Ecol Evol. 2019 Feb;3(2):213-222 - PubMed

References

    1. Oxid Med Cell Longev. 2017;2017:8060949 - PubMed

References

    1. Cell. 2013 Jul 18;154(2):271-3 - PubMed

References

    1. Cardiovasc Ther. 2016 Dec;34(6):404-414 - PubMed

References

    1. Eur J Biochem. 1996 Aug 15;240(1):98-103 - PubMed

References

    1. Biochem Biophys Res Commun. 1983 Jul 29;114(2):670-6 - PubMed

References

    1. Nature. 2018 May;557(7703):101-105 - PubMed

References

    1. Cell. 2016 May 19;165(5):1209-1223 - PubMed

References

    1. Cell. 2015 Oct 22;163(3):560-9 - PubMed

References

    1. Cell. 2016 Aug 11;166(4):802-821 - PubMed

References

    1. Genes Dev. 2008 Dec 1;22(23):3236-41 - PubMed

References

    1. Cell Death Discov. 2017 Sep 11;3:17062 - PubMed

References

    1. Elife. 2016 May 27;5: - PubMed

References

    1. Circulation. 1983 May;67(5):968-77 - PubMed

References

    1. Hum Mutat. 2004 Dec;24(6):460-5 - PubMed

References

    1. Mol Cell. 2015 Apr 2;58(1):123-33 - PubMed

References

    1. Biochem J. 1973 Jul;134(3):707-16 - PubMed

References

    1. Nat Genet. 2007 Apr;39(4):540-3 - PubMed

References

    1. Curr Biol. 2016 Aug 8;26(15):2037-2043 - PubMed

References

    1. Hum Mol Genet. 2004 May 1;13(9):935-44 - PubMed

References

    1. PLoS Genet. 2011 Mar;7(3):e1002028 - PubMed

References

    1. Cell. 2013 Jul 18;154(2):430-41 - PubMed

References

    1. J Biol Chem. 2019 Apr 19;294(16):6621-6634 - PubMed

References

    1. Apoptosis. 2005 Oct;10(5):963-71 - PubMed

References

    1. Cell. 2011 Aug 19;146(4):645-58 - PubMed

References

    1. Nat Rev Mol Cell Biol. 2018 Feb;19(2):109-120 - PubMed

References

    1. Biochem Biophys Res Commun. 2019 May 28;513(2):439-445 - PubMed

References

    1. Cell Metab. 2018 Sep 4;28(3):330-331 - PubMed

References

    1. Eur Heart J. 2014 May;35(18):1172-7 - PubMed

References

    1. Science. 2019 Aug 16;365(6454): - PubMed

References

    1. J Physiol. 2017 Nov 1;595(21):6613-6621 - PubMed

References

    1. Biophys Rep. 2018;4(1):39-49 - PubMed

References

    1. Prog Mol Biol Transl Sci. 2017;146:259-302 - PubMed

References

    1. J Genet Genomics. 2009 Mar;36(3):125-31 - PubMed

References

    1. Br J Pharmacol. 2001 Dec;134(8):1597-9 - PubMed

References

    1. Trends Biochem Sci. 2016 Mar;41(3):261-273 - PubMed

References

    1. Annu Rev Biochem. 2016 Jun 2;85:133-60 - PubMed

References

    1. Trends Genet. 2009 Feb;25(2):91-8 - PubMed

References

    1. Front Genet. 2018 Jul 10;9:225 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10936-41 - PubMed

References

    1. Nature. 2003 May 22;423(6938):456-61 - PubMed

References

    1. Nature. 2011 Sep 25;478(7368):269-73 - PubMed

References

    1. J Theor Biol. 1967 Mar;14(3):255-74 - PubMed

References

    1. PLoS Genet. 2010 Feb 12;6(2):e1000834 - PubMed

References

    1. Psychoneuroendocrinology. 2019 Aug;106:268-276 - PubMed

References

    1. Free Radic Biol Med. 2009 Sep 15;47(6):803-13 - PubMed

References

    1. Curr Biol. 2018 Feb 19;28(4):R170-R185 - PubMed

References

    1. Aging Cell. 2014 Oct;13(5):958-61 - PubMed

References

    1. Arterioscler Thromb Vasc Biol. 2010 Oct;30(10):1940-8 - PubMed

References

    1. Nature. 1990 Jul 26;346(6282):376-9 - PubMed

References

    1. Cell Metab. 2018 Sep 4;28(3):516-524.e7 - PubMed

References

    1. PLoS One. 2012;7(2):e31065 - PubMed

References

    1. Nature. 2004 Oct 21;431(7011):931-45 - PubMed

References

    1. Science. 2012 Aug 3;337(6094):587-90 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):13039-13044 - PubMed

References

    1. Aging (Albany NY). 2018 Jun 10;10(6):1239-1256 - PubMed

References

    1. PLoS Genet. 2013;9(9):e1003794 - PubMed

References

    1. Cell Metab. 2012 May 2;15(5):675-90 - PubMed

References

    1. J Mol Evol. 2003 Sep;57(3):343-54 - PubMed

References

    1. Hum Reprod Update. 2018 Sep 1;24(5):519-534 - PubMed

References

    1. J Biol Chem. 1986 Aug 5;261(22):10340-7 - PubMed

References

    1. Environ Mol Mutagen. 2010 Jun;51(5):440-50 - PubMed

References

    1. PLoS Biol. 2007 May;5(5):e106 - PubMed

References

    1. Front Immunol. 2018 May 04;9:832 - PubMed

References

    1. Curr Biol. 1996 Feb 1;6(2):128-9 - PubMed

References

    1. Am J Physiol Heart Circ Physiol. 2013 Feb 1;304(3):H393-7 - PubMed

References

    1. Sci Rep. 2017 Nov 27;7(1):16357 - PubMed

References

    1. J Investig Med. 2018 Aug;66(6):1019-1022 - PubMed

References

    1. Annu Rev Biochem. 2010;79:683-706 - PubMed

References

    1. PLoS Biol. 2004 Sep;2(9):E273 - PubMed

References

    1. PLoS Genet. 2008 Oct;4(10):e1000237 - PubMed

References

    1. Mol Cell. 2009 May 14;34(4):510-8 - PubMed

References

    1. Mol Gen Genet. 1977 Sep 21;155(1):27-34 - PubMed

References

    1. Sci Rep. 2018 Oct 18;8(1):15347 - PubMed

References

    1. Science. 2019 Dec 20;366(6472):1531-1536 - PubMed

References

    1. Free Radic Biol Med. 2009 Jan 15;46(2):176-81 - PubMed

References

    1. Hum Genet. 2002 Jun;110(6):527-31 - PubMed

References

    1. Science. 2010 Jul 16;329(5989):336-9 - PubMed

References

    1. Aging (Albany NY). 2016 Apr;8(4):796-809 - PubMed

References

    1. Genome Biol Evol. 2014 Sep 22;6(10):2665-80 - PubMed

References

    1. Am J Physiol Renal Physiol. 2019 Nov 1;317(5):F1122-F1131 - PubMed

References

    1. Nat Cell Biol. 2014 Nov;16(11):1035-44 - PubMed

References

    1. Free Radic Biol Med. 2018 Aug 20;124:420-430 - PubMed

References

    1. Atherosclerosis. 2011 Nov;219(1):65-73 - PubMed

References

    1. Cell Syst. 2016 Feb 24;2(2):101-11 - PubMed

References

    1. Cardiovasc Res. 2010 Nov 1;88(2):360-6 - PubMed

References

    1. Nature. 2004 May 27;429(6990):417-23 - PubMed

References

    1. Cold Spring Harb Perspect Biol. 2013 Nov 01;5(11):a021220 - PubMed

References

    1. Cell Metab. 2011 Oct 5;14(4):528-36 - PubMed

References

    1. Genome Res. 2015 Jun;25(6):814-24 - PubMed

References

    1. Science. 2015 Sep 25;349(6255):1449-50 - PubMed

References

    1. Front Genet. 2018 Apr 25;9:144 - PubMed

References

    1. Science. 2013 Sep 6;341(6150):1116-20 - PubMed

References

    1. Nature. 2010 Mar 4;464(7285):104-7 - PubMed

References

    1. Mol Biol Evol. 2016 Dec;33(12):3042-3053 - PubMed

References

    1. Front Genet. 2019 Feb 20;10:130 - PubMed

References

    1. Cell. 2010 Apr 16;141(2):280-9 - PubMed

References

    1. Clin Endocrinol (Oxf). 2019 Aug;91(2):278-287 - PubMed

References

    1. Cell. 2013 Sep 26;155(1):160-71 - PubMed

References

    1. Ann N Y Acad Sci. 2007 Apr;1100:505-9 - PubMed

References

    1. Antioxid Redox Signal. 2005 Sep-Oct;7(9-10):1140-9 - PubMed

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