Thermodynamic Analysis of Mitochondria Working State

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1 PROGRESS IN CHEMISTRY Vol. 18 No. 6 June, ( ),, :O642, Q591,Q731 : A : X(2006) Thermodynamic Analysis of Mitochondria Working State Liu Sha, Liu Huixue, Yang Xiaogai, Yang Xiaoda 3 3 (Department of Chemical Biology &Laboratories of Preventive Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Sciences Center, Bejing , China) Abstract Mitochondria, the plant of energy in cells, has recently received great attention for its roles in metabolic diseases, e. g. diabetes and neural degenerative diseases. In this review, we briefly summarize the major recent progress in the biochemical and relevant studies of mitochondria and discuss comprehensively the working mechanisms and regulations of mitochondria, i. e. the chemiosmosis theory. A novel hypothesis of thermodynamic regulation of mitochondria function is proposed based on the reported results. Key words mitochondria ; chemiosmotic theory ; proton motive force ; ion channels ; thermodynamic analysis [1 ] [1 4 ], ROS (adenosine ROS triphosphate, ATP) ATP [3 6 ],, [7, 8, ] [9 ] Parkinson ( reactive oxygen [10, 11 ] [12 ] species,ros), ROS 95 % [13 ] : , : (No ) 985 (No ) edu. cn

2 Mitochondrion ; 2006 Biochim Biophys. Acta : Mitochondria in Diseases and Therapeutics (Vol. 1762, Issue 2), [15 ] 4 1, 1. 1 NADH, 3 : (NADH2 Q ) ( Q2 c ) ( c ) ATP, (matrix), H +,, ( ) ( ph) 70 %,Taylor [14 ] 615, 498, 9 % 1 [15 ] 2 [14,15 ] 1 Fig. 1 Illustration of structure and some important proteins of [14,15 ] mitochondria 112 ( 2) Fig. 2 Illustration of respiration chain of mitochondria and the standard electric potential for each redox step [15 ] 113 [16, 17 ] ( 1),,, ATP K + ( K ATP ), 1991 [18, 19 ] ATP

3 6 843 : (1), 3 1nmol H + Πmg protein 200mV ( ) ph dependent anion channel, VDAC) [ ] [1 ] mV ph H + : [2 ], Π, ( 10-7 molπl), Ca 2 + Ca 2 + (011molΠL) 10 6 (2) Na + ΠCa 2 + Na + Na + Π H + [1, 3, 4, 16 ] (3) Ca 2 +, ; (uncoupling protein 1, UCP1) [21, 22 ] 2 3 (UCP2, UCP3) [23, 24 ],UCP1 UCP2Π3 UCP UCP ATP,UCPs (voltage Ca [1 4,16 ] Fig. 3 The pathways of Ca 2 + influx and efflux and possible 2 + [1 roles of mitochondrial Ca 4,16 ] 20 % 50 % [25 ] 2 UCP1 [15, 27 ] ; UCP ROS ATP, UCP3 211 UCP2 ATP, ATP ATPΠADP K ATP G Ca 2 +,UCP2 [ ] G > 0 UCP1 G > 0, G < 0 G < ( mitochondrial Ca uniporter, MCU)

4 (coupling), G = - F p = RT[pH - ph ] - F G < 0 ATP : p = ph G > 0 ; G < 0 3 : (1) ATP ATP ATP (2) ADP2ATP, A ATP NADH( reduced form ADP ATP 4 - ADP 3 - of nicotinamide2adenine dinucleotide) (3) ATP, ATP [15, 27 ] [29 ], NADH,( 4 ), [6, 30 ] O 2 (mitochandrial criticality),, ATP :ATP ; ATP, (uncoupling) ATP, (UCP) ATP, 4 ( ) [29 ] Π Fig. 4 The correlation of health state of individual with energy ( 2,4 - DNP ) charge described by arsterial ketone body ratio, AKBR [29 ], 213 ATP ROS 212 ATP [1 ROS ] H + [ Ca 2 + ] m, : (ANT) ATP, ATP ( ) ; ROS, ph ( ph) Ca 2 + (NOS) NO ( p) [28 ],, ROS ROS :

5 6 845 PTP, ATP, c, ATP ( ) ( ROS ) 3 ATP ( ) : 411 (1) = 170mV ph = 015 H + : = ( RTΠzF)Ln [M z+ ] i Π[M z+ ] o : M z z 0 CoQ NADH E 1 = ; K + Na + Ca V,NADH Q 95 molπl ( K + ) 3 molπl, (Na + ) 0104 molπl (Ca 2 + ) : 0, - G 1 = n e F E 1 = n H+ F + RTLn ( a i Πa m ) n e, n H?, F Faraday, a i a m (2) ( ),,, 1nmol H + Πmg protein 200mV ( ), ( G < 0), [20 ph 0105 ] ( 3 mv : ATP ) ( ) ;ATP NADH : a2 0 n e F E 1 = n H+ F + RTLn ( a i Πa m ) n H+ F, ( ) 0 ( n e Πn + H ) E1 4 n e 2, n H 4 I 190mV?? : c (3) CoQHE 0 2 = 0120V (gatekeepers of life and death) [31 ] 4 2? CoQH 2,?, 2, 4 200mV : O 2, c, E 0 3 = 0157V 2,

6 V 3 H ; 190mV 5 ATP P ATP ph,3 Fig. 5 The calculated dependency of ATP synthesis power 190 ( P ATP ) on mitochondrial ph gradient ( ph) 200mV,, ATP,3 ( 44 kjπmol), ATP 150mV ATP ph 3 1 ATP, ph ph ATP mV ph 413 ph, ATP ATP,H + ATP ph ATP ph ATP, 200 mv 0105 ph H +, : ph K +,H + ATP K + ( K ATP ), ATP ph K ATP ; ph K + ATP,ATP ph H + ( P) ATP,H + H + : P = U I = i (H + ) = b [ H + ] ( b ) p = ph, : P = b (10 - ph outer ph inter ) ( p ph) ph = 7120 ATP P ATP ph 5 UCPs K + ΠH + ph UCPs, UCP1 UCP2Π3, UCP1 ;UCP1 ph 414,ATP, ph = 018, 168 mv ph 0175, ( 6) : ATP ATP ; ph

7 6 847 c, 6, Fig. 6 The proposed mechanism of regulation of mitochondrial ph function by cross membrane proton gradient, K ATP ATP ph : ATP, ATP K ATP [13, 33 ] 3, ph ATP, 3 Ca 2 +,, ph ( ) Alzheimer K ATP, ATP, [13 K ATP ] ( ) 415,, ATP 3 Ca 2 + [34 ] [ Ca 2 + ] m ATP :,Ca 2 +,[ Ca 2 + ] m,cu + ΠCu 2 + Ca 2 +,Ca 2 +, [ Ca 2 + ] m (2) Ca 2 + : Ln 3 + Sr 2 + VO 2 + Ca 2 + ROS (3) K + : Cs + Li + K + ROS Ca 2 + PTP ROS Ca 2 + PTP Ca 2 + ATP ATP [32 ] : ph ; ATP, (1) H + : (Cu + ΠCu 2 + ) 3 - (4) PO 4 : K ATP, ATP,

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