Complex I dysfunction redirects cellular and mitochondrial metabolism in Arabidopsis.
Mitochondrial complex I is a major avenue for reduced NAD oxidation linked to oxidative phosphorylation in plants. However, the plant enzyme has structural and functional features that set it apart from its counterparts in other organisms, raising questions about the physiological significance of this complex in plants. We have developed an experimental model in which rotenone, a classic complex I inhibitor, has been applied to Arabidopsis (Arabidopsis thaliana) cell suspension cultures in order to dissect early metabolic adjustments involved in cell acclimation to mitochondrial dysfunction. Rotenone induced a transitory decrease in cellular respiration (0-4 h after treatment). Cell respiration then progressively recovered and reached a steady state at 10 to 12 h after treatment. Complex I inhibition by rotenone did not induce obvious oxidative stress or cell death but affected longer term cell growth. Integrated analyses of gene expression, the mitochondrial proteome, and changes in primary metabolism indicated that rotenone treatment caused changes in mitochondrial function via alterations in specific components. A physical disengagement of glycolytic activities associated with the mitochondrial outer membrane was observed, and the tricarboxylic acid cycle was altered. Amino acid and organic acid pools were also modified by rotenone treatment, with a marked early decrease of 2-oxoglutarate, aspartate, and glutamine pools. These data demonstrate that, in Arabidopsis cells, complex I inhibition by rotenone induces significant remodeling of metabolic pathways involving the mitochondria and other compartments and point to early metabolic changes in response to mitochondrial dysfunction.
Garmier
Marie
M
Australian Research Council Centre of Excellence in Plant Energy Biology M316, University of Western Australia, Crawley, Western Australia 6009, Australia.
Carroll
Adam J
AJ
Delannoy
Etienne
E
Vallet
Corinne
C
Day
David A
DA
Small
Ian D
ID
Millar
A Harvey
AH
D017360:Arabidopsis / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012402:Rotenone / Q000494:pharmacology
D004791:Enzyme Inhibitors; D012402:Rotenone; D009247:NADH, NADPH Oxidoreductases
Plant Physiol. 2003 Jan;131(1):264-75
12529534
Mitochondrion. 2007 May;7(3):177-94
17320492
Plant J. 2004 Mar;37(6):914-39
14996223
FEBS Lett. 2003 Jul 17;547(1-3):125-30
12860399
Plant J. 1996 Mar;9(3):357-68
8919912
Plant Mol Biol. 2002 Nov;50(4-5):735-42
12374304
Plant J. 2006 Sep;47(5):751-60
16923016
Plant Physiol. 2001 Dec;127(4):1711-27
11743115
Eur J Biochem. 1991 Dec 5;202(2):617-23
1722151
Front Biosci. 2007 Jan 01;12:986-1007
17127354
Nat Neurosci. 2000 Dec;3(12):1301-6
11100151
J Mol Biol. 2005 Jul 8;350(2):263-77
15935378
Proc Natl Acad Sci U S A. 2006 May 16;103(20):7607-12
16682634
Annu Rev Plant Biol. 2004;55:23-39
15725055
Plant Mol Biol. 1997 Nov;35(5):585-96
9349280
Annu Rev Genet. 2006;40:159-85
16771627
Biochem J. 1999 Oct 15;343 Pt 2:327-34
10510296
Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3225-9
15713802
Plant Physiol. 2005 Sep;139(1):64-78
16126851
FEBS Lett. 1995 Oct 16;373(3):307-9
7589489
Plant J. 2007 Nov;52(4):763-78
17883376
Electrophoresis. 1997 Oct;18(11):2059-64
9420170
Plant J. 2002 Dec;32(6):891-904
12492832
FEBS Lett. 2001 Nov 16;508(2):272-6
11718729
Biochim Biophys Acta. 2003 Jul 10;1604(3):159-69
12837548
Plant Mol Biol. 2004 Sep;56(1):77-90
15604729
J Biol Chem. 2005 Jul 15;280(28):25994-6001
15849190
Plant Physiol. 1990 Nov;94(3):1012-8
16667790
Plant Mol Biol. 2007 Jun;64(3):319-27
17406791
Plant Cell. 2007 Feb;19(2):640-55
17277035
Plant Physiol. 2004 Feb;134(2):777-89
14730085
J Biol Chem. 2004 May 14;279(20):20672-7
15016808
FEBS Lett. 2003 Jun 12;545(1):9-17
12788486
Mol Cell Proteomics. 2005 Aug;4(8):1122-33
15914488
Plant Physiol. 2004 Apr;134(4):1450-9
15064371
Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3436-41
9096412
Plant Physiol. 2000 Nov;124(3):1239-50
11080300
Plant Cell. 2003 Sep;15(9):2140-51
12953116
Bioinformatics. 2005 Apr 15;21(8):1635-8
15613389
Methods Enzymol. 1979;55:454-62
223000
Biosci Biotechnol Biochem. 2002 Sep;66(9):1925-9
12400692
N Engl J Med. 2003 Jun 26;348(26):2656-68
12826641
Biochim Biophys Acta. 1998 Jan 27;1363(1):59-69
9526046
Plant Cell. 2002 Dec;14(12):3271-84
12468742
Trends Plant Sci. 2007 Mar;12(3):125-34
17293156
Plant Cell. 2003 May;15(5):1212-26
12724545
Plant Cell. 2007 Nov;19(11):3723-38
17981998
Plant Physiol. 2003 Oct;133(2):683-92
14512520
Mol Cell Biol. 1999 Oct;19(10):6720-8
10490611
Plant Mol Biol. 2005 May;58(2):193-212
16027974
Mol Microbiol. 2005 Sep;57(5):1265-87
16102000
Plant Physiol. 2003 Oct;133(2):443-7
14555771
Plant Cell. 2006 Sep;18(9):2112-21
16968907
Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):8271-6
10393984
Plant Cell. 2007 Oct;19(10):3256-65
17965268
Plant Physiol. 1989 Apr;89(4):1311-7
16666702
J Biol Chem. 2007 May 25;282(21):15619-31
17383966