Table 1.
C. elegans gene | Human Ortholog |
Life Extension * |
Method of Knockdown |
Reference ** |
---|---|---|---|---|
COMPLEX I | ||||
K09A9.5 (gas-1) | NDUFS2 | decrease | genetic | [1, 2, 3‡] |
ZK973.10 (lpd-5) | NDUFS4 | |||
T26A5.3 (nduf-2.2) | NDUFS2 | √ | RNAi | [4] |
Y54E10BL.5 (nduf-5) | NDUFS5 | |||
F22D6.4 (nduf-6) | NDUFS6 | |||
W10D5.2 (nduf-7) | NDUFS7 | |||
C09H10.3 (nuo-1) | NDUFV1 | √ | genetic & RNAi | [5, 6‡, 7‡, 8] |
T10E9.7 (nuo-2) | NDUFS3 | √ | RNAi | [9, 10, 11] |
Y57G11C.12 (nuo-3) | NDUFA6 | √ | RNAi | [4, 7‡, 10] |
K04G7.4 (nuo-4) | NDUFA10 | √ | RNAi | [4, 10, 12‡] |
Y45G12B.1 (nuo-5) | NDUFS1 | √ | RNAi | [10] |
W01A8.4 (nuo-6) | NDUFB4 | √ | genetic & RNAi | [13] |
C16A3.5 | NDUFB9 | |||
C18E9.4 | NDUFB3 | √ | RNAi | [7‡] |
C25H3.9 | NDUFB5 | √ | RNAi | [7‡] |
C33A12.1 | NDUFA5 | √ | RNAi | [4, 7‡] |
C34B2.8 | NDUFA13 | |||
D2030.4 | NDUFB7 | √ | RNAi | [12‡, 14‡] |
F31D4.9 | NDUFA1 | |||
F37C12.3 | NDUFAB1 | |||
F42G8.10 | NDUFB11 | |||
F44G4.2 | NDUFB2 | |||
F45H10.3 | NDUFA7 | |||
F53F4.10 | NDUFV2 | |||
F59C6.5 | NDUFB10 | √ | RNAi | [5‡] |
T20H4.5 | NDUFS8 | √ | RNAi | [4, 12‡] |
Y51H1A.3 | NDUFB8 | |||
Y53G8AL.2 | NDUFA9 | √ | RNAi | [4] |
Y54F10AM.5 | NDUFA8 | |||
Y56A3A.19 | NDUFAB1 | √ | RNAi | [4, 5‡] |
Y63D3A.7 | NDUFA2 | |||
Y71H2AM.4 | NDUFC2 | √ | RNAi | [4] |
Y94H6A.8 | NDUFA12 | |||
ZK809.3 | NDUFB6 | √ | RNAi | [4] |
COMPLEX II | ||||
C03G5.1 (sdha-1) | SDHA | no effect | RNAi | [2, 15‡] |
C34B2.7 (sdha-2) | SDHA | no effect | RNAi | [2, 15‡] |
F42A8.2 (sdhb-1) | SDHB | no effect | RNAi | [2, 7‡, 15‡] |
T07C4.7 (mev-1) | SDHC | decrease | genetic & RNAi | [2, 11, 15‡, 16] |
F33A8.5 (sdhd-1) | SDHD | no effect | RNAi | [2, 15‡] |
COMPLEX III | ||||
C54G4.8 (cyc-1) | CYC1 | √ | RNAi | [7‡, 9, 10, 17] |
E04A4.7 (cyc-2.1) | CYCS (cytochrome c) | √ | RNAi | [4] |
ZC116.2 (cyc-2.2) | CYCS (cytochrome c) | |||
F42G8.12 (isp-1) | UQCRFS1 | √ | genetic & RNAi | [11, 17] |
F56D2.1 (ucr-1) | UQCRC1 | √ | RNAi | [4, 7‡] |
VW06B3R.1 (ucr-2.1) | UQCR2 | |||
T10B10.2 (ucr-2.2) | UQCR2 | no effect | RNAi | [7‡] |
T24C4.1 (ucr-2.3) | UQCR2 | decrease | genetic & RNAi | [7‡, 18] |
F45H10.2 | UQCRQ | √ | RNAi | [4] |
F57B10.14 | UQCR11 | |||
R07E4.3 | UQCRQ | √ | RNAi | [7‡] |
T02H6.11 | UQCRB | √ | RNAi | [7‡, 14‡] |
T27E9.2 | UQCRH | √ | RNAi | [7‡] |
COMPLEX IV | ||||
F26E4.9 (cco-1) | COX5B | √ | RNAi | [4, 7‡, 9, 10, 11, 12‡, 14‡, 17] |
Y37D8A.14 (cco-2) | COX5A | √ | RNAi | [7‡, 10, 19] |
F26E4.6 (cco-4) | COX7C | √ | RNAi | [5‡, 7‡, 12‡, 14‡] |
F29C4.2 | COX6C | √ | RNAi | [4, 7‡] |
F40G9.2 | COX17 | |||
F54D8.2 | COX6A1 | √ | RNAi | [4, 7‡] |
JC8.5 | COX11 | |||
T06D8.5 | COX15 | √ | RNAi | [14] |
W09C5.8 | COX4 | √ | RNAi | [4, 7‡, 12, 14] |
Y46G5A.2 | COX10 | |||
Y71H2AM.5 | COX6B | √ | RNAi | [7‡] |
COMPLEX V | ||||
F35G12.10 (asb-1) | ATP5F1 (b) | |||
F02E8.1 (asb-2) | ATP5F1 (b) | √ | RNAi | [10] |
K07A12.3 (asg-1) | ATP5L (g) | |||
C53B7.4 (asg-2) | ATP5L (g) | √ | RNAi | [12‡] |
C34E10.6 (atp-2) | ATP5B (β) | √ | genetic & RNAi | [5, 6‡] |
F27C1.7 (atp-3) | ATP5O (OSCP) | √ | RNAi | [9, 10, 11] |
T05H4.12 (atp-4) | ATP5J (F6) | √ | RNAi | [10] |
C06H2.1 (atp-5) | ATP5H (d) | √ | RNAi | [10] |
F32D1.2 (hpo-18) | ATP5E (ε) | |||
F58F12.1 | ATP5D (δ) | |||
H28O16.1 | ATP5A1 (α) | √ | RNAi | [5] |
R04F11.2 | ATP5I (e) | |||
R05D3.6 | ATP5E (ε) | |||
R53.4 | ATP5J2 (f) | |||
T26E3.7 | ATP5A1 (α) | |||
Y69A2AR.18 | ATP5C1 (γ) | |||
Y82E9BR.3 | ATP5G3 (c) | |||
ZC262.5 | ATP5E (ε) | |||
OTHER ± | ||||
T06D8.6 (cchl-1) | HCCS | √ | RNAi | [4] |
ZC395.2 (clk-1) | COQ7 | √ | genetic | [20] |
F59G1.7 (frh-1) | FXN | √ | genetic & RNAi | [11, 21, 22] |
ZC395.6 (gro-1) | TRIT1 | √ | genetic | [23] |
C37H5.8 (hsp-6) | mtHSP70 | √ | RNAi | [22] |
ZK524.3 (lrs-2) | LARS2 | √ | genetic | [14‡] |
T21C9.1 (mics-1) | OMP25 | √ | genetic & RNAi | [24‡] |
F56B3.8 (mrpl-2) | MRPL2 | √ | RNAi | [25‡] |
W09D10.3 (mrpl-12) | MRPL12 | √ | RNAi | [4] |
Y48E1B.5 (mrpl-37) | MRPL37 | √ | RNAi | [25‡] |
B0261.4 (mrpl-47) | MRPL47 | √ | RNAi | [14‡] |
E02A10.1 (mrps-5) | MRPS5 | √ | RNAi | [25‡] |
F09G8.3 (mrps-9) | MRPS9 | √ | RNAi | [4] |
Y37D8A.18 (mrps-10) | MRPS10 | √ | RNAi | [4] |
F21D5.8 (mrps-33) | MRPS33 | √ | RNAi | [4] |
F43E2.7 (mtch-1) | MTCH1 | √ | RNAi | [5‡] |
F10D11.1 (sod-2) | SOD2 (MnSOD) | √ | genetic | [26‡] |
C08A9.1 (sod-3) | SOD2 (MnSOD) | no effect | genetic | [26‡] |
ZK637.9 (tpk-1) | TPK1 | √ | genetic | [4] |
K08F11.4 (yars-1) | YARS2 | √ | RNAi | [4] |
F13G3.7 | SLC25A44 | √ | RNAi | [14‡] |
K01C8.7 | SLC25A32 | √ | RNAi | [14‡] |
Blank space indicates nothing has been reported to date.
List is not exhaustive.
Numbers refer to references listed below.
FUdR used.
Hartman, P.S., et al., Mitochondrial mutations differentially affect aging, mutability and anesthetic sensitivity in Caenorhabditis elegans. Mech Ageing Dev, 2001. 122(11): p. 1187–201.
Pujol, C., et al., Succinate dehydrogenase upregulation destabilize complex I and limits the lifespan of gas-1 mutant. PLoS One, 2013. 8(3): p. e59493.
Van Raamsdonk, J.M. and S. Hekimi, FUdR causes a twofold increase in the lifespan of the mitochondrial mutant gas-1. Mech Ageing Dev, 2011. 132(10): p. 519–21.
Kim, Y. and H. Sun, Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan. Aging Cell, 2007. 6(4): p. 489–503.
Curran, S.P. and G. Ruvkun, Lifespan regulation by evolutionarily conserved genes essential for viability. PLoS Genet, 2007. 3(4): p. e56.
Tsang, W.Y., et al., Mitochondrial respiratory chain deficiency in Caenorhabditis elegans results in developmental arrest and increased life span. J Biol Chem, 2001. 276(34): p. 32240–6.
Zuryn, S., et al., Mitochondrial dysfunction in Caenorhabditis elegans causes metabolic restructuring, but this is not linked to longevity. Mech Ageing Dev, 2010. 131(9): p. 554–61.
Grad, L.I. and B.D. Lemire, Mitochondrial complex I mutations in Caenorhabditis elegans produce cytochrome c oxidase deficiency, oxidative stress and vitamin-responsive lactic acidosis. Hum Mol Genet, 2004. 13(3): p. 303–14.
Dillin, A., et al., Rates of behavior and aging specified by mitochondrial function during development. Science, 2002. 298(5602): p. 2398–401.
Hansen, M., et al., New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genet, 2005. 1(1): p. 119–28.
Rea, S.L., N. Ventura, and T.E. Johnson, Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans. PLoS Biol, 2007. 5(10): p. e259.
Hamilton, B., et al., A systematic RNAi screen for longevity genes in C. elegans. Genes Dev, 2005. 19(13): p. 1544–55.
Yang, W. and S. Hekimi, Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegans. Aging Cell, 2010. 9(3): p. 433–47.
Lee, S.S., et al., A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity. Nat Genet, 2003. 33(1): p. 40–8.
Kuang, J. and P.R. Ebert, The failure to extend lifespan via disruption of complex II is linked to preservation of dynamic control of energy metabolism. Mitochondrion, 2012. 12(2): p. 280–7.
Ishii, N., et al., A methyl viologen-sensitive mutant of the nematode Caenorhabditis elegans. Mutat Res, 1990. 237(3–4): p. 165–71.
Feng, J., F. Bussiere, and S. Hekimi, Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev Cell, 2001. 1(5): p. 633–44.
Butler, J.A., et al., Long-lived mitochondrial (Mit) mutants of Caenorhabditis elegans utilize a novel metabolism. FASEB J, 2010. 24(12): p. 4977–88.
Suthammarak, W., et al., Complex I function is defective in complex IV-deficient Caenorhabditis elegans. J Biol Chem, 2009. 284(10): p. 6425–35.
Wong, A., P. Boutis, and S. Hekimi, Mutations in the clk-1 gene of Caenorhabditis elegans affect developmental and behavioral timing. Genetics, 1995. 139(3): p. 1247–59.
Ventura, N., et al., Reduced expression of frataxin extends the lifespan of Caenorhabditis elegans. Aging Cell, 2005. 4(2): p. 109–12.
Ventura, N. and S.L. Rea, Caenorhabditis elegans mitochondrial mutants as an investigative tool to study human neurodegenerative diseases associated with mitochondrial dysfunction. Biotechnol J, 2007. 2(5): p. 584–95.
Lakowski, B. and S. Hekimi, Determination of life-span in Caenorhabditis elegans by four clock genes. Science, 1996. 272(5264): p. 1010–3.
Hoffmann, M., et al., MICS-1 interacts with mitochondrial ATAD-3 and modulates lifespan in C. elegans. Exp Gerontol, 2012. 47(3): p. 270–5.
Houtkooper, R.H., et al., Mitonuclear protein imbalance as a conserved longevity mechanism. Nature, 2013. 497(7450): p. 451–7.
Van Raamsdonk, J.M. and S. Hekimi, Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet, 2009. 5(2): p. e1000361.