1. Oxidative phosphorylation
Electro-transfer reaction in mitochondria
ATP synthesis
氧化磷酸化反應:
1粒線體中的電子傳遞反應
2 ATP的合成
Regulation of oxidative phosphorylation
氧化磷酸化反應的調節

2. In eukaryotes, oxidative phosphorylation occurs in mitochondria
Oxidative phosphorylation involves the reduction of O2 to H2O with electrons donated by NADH and FADH2, and occurs equally well in light or darkness.
真核細胞，氧化磷酸化反應發生在粒線體，日夜皆在進行。是將NADH and FADH2與O2氧化還原成水，釋出的能量轉換ATP的作用。

3. Our current understanding of ATP synthesis in mitochondria and chloroplasts is based on the hypothesis , introduced by Peter Mitchell in 1961, that transmembrane differences in proton concentration are the reservoir for the energy extracted from biological oxidation reaction.
ATP的合成是遵守化學滲透偶合理論方式進行
This chemiosmotic theory has been accepted as one of the great unifying principles of twentieth century biology.

4. Electron-transfer reactions in mitochondria
The discovery in 1948 by Eugene Kennedy and Albert Lehninger that mitochondria are the site of oxidative phosphorylation in eukaryotes.
1948年Eugene Kennedy and Albert Lehninger 發現真核細胞，氧化磷酸化反應發生在粒線體。

5. Biochemical anatomy of a mitochondrion
粒線體的生物構造

6. Mitochondria have two membranes
Mitochondria have two membranes. The outer mitochondrial membrane is readily permeable to small molecules (Mr < 5000) and ions, which move freely through transmembrane channel called porins.
粒線體有兩層膜，外膜可通透小分子(Mr < 5000)與離子。

7. The inner membrane is impermeable to most small molecules and ions, including protons; the only species that cross the inner membrane are those for which there are specific transporters.
內膜則無法通透小分子(Mr < 5000)與離子與蛋白質。需透過蛋白輸送器(protein transporters)才行。

8. Electrons are funneled to university electron acceptors
Oxidative phosphorylation begins with the entry of electrons into the respiratory chain.
氧化磷酸化反應始於電子進入吸收傳遞鏈
universal electron acceptors-nicotinamide nucleotides (NAD+ or NADP+) or flavin nucleotides (FMN or FAD).
nicotinamide nucleotides(NAD+ or NADP+) 或 flavin nucleotides (FMN or FAD)是暫時接受者。

10. NADH and NADPH are water-soluble electron carriers that associate reversibly with dehydrogenases. NADH 與 NADPH是水溶性的電子攜帶者，且與dehydrogenase可逆結合。
Neither NADH nor NADPH can cross the inner mitochondrial membrane, but the electrons they carry can be shuttled across indirectly. NADH 與 NADPH是無法通過粒線內膜，但電子可經由間接的管道進入。

11. Flavoproteins contain a very tightly, sometimes covalently, bound flavin nucleotide, either FMN or FAD.
The oxidized flavin nucleotide can accept either one electron (yielding the semiquinone form) or two (yielding FADH2 or FMNH2).
黃素蛋白上會共價結合FMN 或FAD，至多可結合兩個電子。

12. Ubiquinone also called coenzyme Q, or simply Q.
is a lipid-soluble benzoquinone with a long isoprenoid side chain.
Coenzyme Q是油性的benzoquinone共價結合長鏈的異戊二烯(一般約重複9-10次)稱Q9或Q10

13. Ubiquinone can accept one electron to become the semiquinone radical (QH·) or two electrons to form ubiquinol (QH2) and , like flavoprotein carriers, it can act at the junction between a two-electron donor and one-electron acceptor.

14. Cytochromes 細胞色素蛋白
Are proteins with characteristic strong absorption of visible light, due to their iron-containing heme prosthetic groups.
細胞色素蛋白是含血基質(heme)與鐵的蛋白
Mitochondria contain three classes of cytochromes, designated a, b and c, distinguished by differences in their light-absorption spectra.
粒線體含三種細胞色素蛋白稱cytochromes a, b and c，是因其吸光性質不同而區分。

15. The longest-wavelength band is near 600 nm in type a cytochromes, near 560 nm in type b, and near 550 nm in type c. The heme cofactors of a and b cytochromes are tightly, but not covalently, bound to their associated proteins; the hemes of c-type cytochromes are covalently attached through Cys residues.
Cytochromes a與b中的heme與蛋白緊密結合， cytochromes c中的heme則與蛋白共價結合。

16. Absorption spectra of cytochrome c in its oxidized (red) and reduced (blue) forms. Also labeled are the characteristic a, b, and g bands of the reduced form.

17. Prosthetic groups of cytochromes
Prosthetic groups of cytochromes. Each consists of four five-membered, nitrogen-containing rings in a cyclic structure called a porphyrin. The four nitrogen atoms are coordinated with a central Fe ion, either Fe2+ or Fe3+.

18. Iron-sulfur centers硫鐵蛋白

19. 圖10.1 電子傳遞鏈

21. Methods for determining the sequence of electron carriers
還原半電位表

22. 圖10.9 粒線體中電子傳遞鏈的能量關係

23. 圖10.10 ㄧ些粒線體電子傳遞鏈的抑制劑

24. In the presence of an electron donor and O2, each inhibitor causes a characteristic pattern of oxidized/reduced carriers; those before the block become reduced (blue), and those after the block become oxidized (red).電子傳遞鏈中電子傳遞順序與其阻斷劑。

25. Electron carriers function in multienzyme complexes
The electron carriers of the respiratory chain are organized into membrane-embedded supramolecular complexes that can be physically separated.呼吸鏈的電子攜帶者是位於膜中的巨大蛋白複合物，且可分離出。

26. Separation of functional complexes of the respiratory chain 分離呼吸鏈具功能的複合體

29. Electron-transferring
flavoprotein (ETF)
Path of electrons from NADH, succinate, fatty acyl-CoA, and glycerol 3-phosphate to ubiquinone.電子的傳遞路徑

30. NADH:ubiquinone oxidoreductase (or NADH dehydrogenase) (complex I)複合體I

31. Complex I: NADH to Ubiquinone
Complex I is also called NADH:ubiquinone oxidoreductase or NADH dehydrogenase.
複合體I又稱NADH:ubiquinone oxidoreductase 或 NADH dehydrogenase
Complex I is a large enzyme composed of 42 different polypeptide chains, including an FMN-containing flavoprotein and at least six iron-sulfur centers.
Complex I是一個巨大酵素體，含FMN的黃素蛋白與硫鐵蛋白。

32. Complex I catalyzes two simultaneous and obligately coupled processes:
(1) the exergonic transfer to ubiquinone of a hydride ion from NADH and a proton from the matrix:
NADH + H+ + Q  NAD+ + QH2
(2) the endergonic transfer of four protons from the matrix to the intermembrane space.
Complex I同時具兩種作用:1電子傳遞。2質子的輸送。

33. Ubiquinol (QH2)
Ubiquinol (QH2) diffuses in the inner mitochondrial membrane from Complex I to ComplexIII, where it is oxidized to Q in a process that also involves the outward movement of H+.
Ubiquinol (QH2)將電子傳給Complex III

35. Complex II: Succinate to Ubiquinone
Complex II also called as succinate dehydrogenase, the only membrane-bound enzyme in the citric acid cycle.
Complex II contains five prosthetic groups of and four different protein subunits.
複合體 II又稱succinate dehydrogenase，是TCA cycle中唯一的膜蛋白複合體，含硫鐵，血基質與FAD等輔基。

36. Structure of Complex II

37. Other substrates for mitochondrial dehydrogenase pass electrons into the respiratory chain at the level of ubiquinone, but not through Complex II

38. Complex III: Ubiquinone to cytochrome c
Complex III is also called cytochrome bc1 complex or ubquinone:cytochrome c oxidoreductase.
Complex III又稱cytochrome bc1 complex or ubquinone:cytochrome c oxidoreductase.亦具兩種作用:1電子傳遞。2質子的輸送。
Complex III couples the transfer of electrons from ubiquinol to cytochrome c with the vectorial transport of protons from matrix to the intermembrane space.

39. Complex IV: Cytochrome c to O2
Complex IV is also called cytochrome oxidase and carries electrons from cytochrome c to molecular oxygen, reducig it to H2O.
Complex IV is a large enzyme of the inner mitochondrial membrane.
Complex IV 又稱 cytochrome oxidase攜帶來至cytochrome c的電子催化產生水。

40. Path of electrons through Complex IV

41. The overall reaction catalyzed by Complex IV
4 Cyt c (reduced) + 8H+ + O2 →
4 cyt c (oxidized) + 4 H+ + 2 H2O
Complex IV含銅離子，亦具兩種作用:1電子傳遞。2質子的輸送。 N P

42. The vectorial equation for the process is:
Summary of the flow of electrons and protons through the four complexes of the respiratory chain
The vectorial equation for the process is:
NADH + 11H O2 → NAD+ + 10H+ + H2O N P

43. 圖10.12 化學滲透模型的概觀

44. Proton-motive force 質子趨動力
The energy of electron transfer is efficiently conserved in a proton gradient, termed the proton-motive force.
質子趨動力:電子傳遞的能量儲存於質子梯度中。

45. It has two components:
The chemical potential energy due to the difference in concentration of a chemical species (H+) in the two regions separated by the membrane.
化學位能由於膜兩邊不同的質子濃度所形成。
The electrical potential energy that results from the separation of charge when a proton moves across the membrane without a counterion.
電位能造成膜兩邊質子濃度不同。

46. Proton-motive force

47. The free-energy change for the creation of an electrochemical gradient by an ion pump
膜兩邊的質子梯度所產生的自由能
ΔG = RT ln (C2/C1) + Z FΔY
For protons at 25°C
In(C2/C1) = 2.3 (log [H+]P – log [H+]N)
= 2.3 (pHN-pHP) = 2.3 ΔpH
Thus, ΔG = 2.3 RT ΔpH + FΔY
= (5.70 kJ/mol) ΔpH +(96.5 kJ/Vmol) ΔY
ΔY是膜電位差

48. Because the transfer of two electrons from NADH to O2 is accompanied by the outward pumping of 10 H+, roughly 200 kJ of 220 kJ released by oxidation of a mole of NADH is conserved in the proton gradient.
估算1 mole NADH約可打出10 mole個質子，花費約 kj 的能量。

49. ATP Synthesis The chemiosmotic model was proposed by Peter Michell.
The proton-motive force drives the synthesis of ATP as protons flow passively back into the matrix through a proton pore associated with ATP synthase. 質子趨動力趨動質子經由內膜上的質子洞(是一個ATP合成酶)流回基質，並偶合ATP的合成。

50. Chemiosomitic model

51. Coupling of electron transfer and ATP synthesis in mitochondria
When isolated mitochondria are suspended in a buffer containing ADP and Pi, and an oxidizable substrate such as succinate, three measured processes occur: (1) the substrate is oxidized (succinate yields furmarate), (2) O2 is consumed, and (3) ATP is synthesized.將質子粒線體置於含有ADP 與 Pi 與氧化受質 (an oxidizable substrate)如琥珀酸後，三件測量的結果會發生: (1) 產生延胡索酸 (2)氧氣消耗(3)ATP被合成。

52. Coupling of electron transfer and ATP synthesis in mitochondria
When isolated mitochondria are suspended in a buffer containing ADP and Pi, and an oxidizable substrate such as succinate, three measured processes occur: (1) the substrate is oxidized (succinate yields furmarate), (2) O2 is consumed, and (3) ATP is synthesized.將質子粒線體置於含有ADP 與 Pi 與氧化受質 (an oxidizable substrate)如琥珀酸後，三件測量的結果會發生: (1) 產生延胡索酸 (2)氧氣消耗(3)ATP被合成。

53. Certain reagents can uncouple oxidation from phosphorylation
Chemical uncouplers include DNP and FCCP, weak acids with hydrophobic properties that permit them to diffuse readily across mitochondroal membrane.
一些去偶合劑(uncouplers)如DNP與FCCP，具弱酸與疏水性可穿膜破壞質子梯度的試劑。

54. After entering the matrix in the protonated form, they can release a proton, thus dissipating the proton gradient.
去偶合劑可進入基質並釋放質，因此會破壞內膜內外的質子梯度。

55. Two chemical uncouplers of oxidative phosphorylation

56. ATP synthase
Mitochondrial ATP synthase is an F-type ATPase. It, called Complex V, has two distinct components: F1, a peripherial membrane protein, and Fo (o denoting oligomycin-sensitive), which is integral to the membrane. F1, the first factor recognized as essential for oxidative and purified by Efraim Racker and his colleagues.
粒線體ATP synthase 是屬於F型ATP synthase，
: F1是膜週邊蛋白(1表第一個被Efraim Racker 團隊純化出的氧化因子)，Fo (O denoting oligomycin-sensitive)，是穿膜蛋白。

57. ATPase localized on the inner mitochondrial membrane catalyzes the formation of ATP from ADP and Pi, accompanied by the flow of protons from the P to the N sdie of the membrane.
ATPase位於粒線體內膜，質子的流進伴隨ATP的合成

58. What accounts for the huge difference?
ATP synthase stabilizes ATP relative to ADP + Pi by binding ATP more tightly, releasing enough energy to counterbalance the cost of making ATP. ATP合成酶與ATP結合力很強，遠大與ADP或 Pi 的結合。
Measurements of binding constants show that FoF1 binds ATP with very high affinity (Kd ≦10-12 M) and ADP with much lower affinity (Kd ≒10-5 M).
The difference in Kd corresponds to a difference of about 40 kJ/mol in binding energy, and this binding energy drives the equilibrium toward formation of the product ATP.由於結合力的不同，造成約40 kJ/mol差異，使得反應傾向ATP形成。

59. The proton gradient drives the release of ATP from the enzyme surface.

60. Mitochondrial production and disposal of superoxide(超氧歧的生成與清除)
The passage of electrons from QH2 to cytochrome bL through Complex III, and passage of electrons from Complex I to QH2, involve the radical as intermediate. The Q can, with a low probability, pass an electron to O2 in the reaction
O2 + e- →
粒線體會產生superoxide:在電子傳遞的過程中，電子會由複合體漏出與氧結合形成超氧歧(superoxide ·O2- ) . . _ - Q . - O2

61. The superoxide free radical generated, ·O2- is very reactive and can damage enzymes, membrane lipids, and nucleic acids.
Superoxide含自由基對酵素、膜與核酸具破壞性。

62. Reactive oxygen species (ROS)
ROS包含Superoxide radical (．O2- )、hydrogen peroxide (H2O2)、hydroxyl radical (．OH)與singlet oxygen( 1Ｏ2 )。因為ROS相當reactive，易引起一些鏈鎖反應。如lipid peroxidation reaction: hydroxyl radical會攻擊一些脂肪酸，引起鏈鎖反應。食品加工時常會促進這種radical chain reaction，常需加入抗氧化劑，阻止radical chain reaction的反應。

63. 反應性氧化物
游離子(radical)

64. 一些細胞為特殊的需要也會合成ROS
例如代謝xenobiotics(foreign molecule)與respiratory burst。respiratory burst是白血球細胞胞利用來殺死細菌的機制。是一個ROS具破壞性的例子。當吞噬細胞結合細菌後，會提高O2的消耗近100倍，位於Phagolysome Membrane的NADPH oxidase會將O2轉成superoxide radical (．O2- )。

65. 圖10.19 游離子連鎖反應

66. 圖10.20 呼吸爆發現象

67. Mitochondrial production and disposal of superoxide
Antimycin A, an inhibitor of Complex III, may act by occuping the QN site, thus blocking the Q cycle and prolonging the binding of Q to the QP site; this would increase the likelihood of superoxide radical formation and cellular damage.
Antimycin A是Complex III的抑制劑，能阻斷電子的傳遞，造成自由基增加與細胞的損壞。 . -

68. From 0.1% to as much as 4% of the ·O2- used by actively respiring mitochondria form O2 —more than enough to have lethal effects on a cell unless the free radical is quickly disposal of.
有氧代謝約產生氧量的0.1% 至 4% 之·O2-。超過此量時具致命性，除非自由基能快速分解。

69. Disposal of superoxide. -
To prevent oxidative damage by O2, cell have several forms of the enzyme superoxide dismutase, which catalyzes the reaction
2 O H+ → H2O2 + O2
The hydrogen peroxide (H2O2) generated by superoxide dimutase is rendered harmless by the action of glutathione peroxidase.
superoxide dimutase (超氧歧化酶)可清除superoxide轉換成過氧化氫(H2O2)。 glutathione peroxidase可將(H2O2)轉換成無害的O2 . -

70. Catalase:是一個含heme的酵素
催化: 2 H2O H2O + O2 ， RH2 + H2O R + 2 H2O
Glutathione peroxidase: 是一個含Selenium的酵素，也是控制細胞過氧化物濃度的重要酵素。
催化: 2 GSH + ROOH GSSG + ROH + H2O
2 H2O H2O + O2

71. Glutathione peroxidase is remarkable for the presence of a selenocysteine residue, in which an atom of selenium replaces the sufur atom. The selenol group (-SeH) is more acidic the thiole (-SH); its pKa is about 5, so at neutral pH, the selenocysteine side chain is essentially fully oxidized (-CH2Se-).
Glutathione peroxidase是含硒的酶

72. 圖10.21麩胱甘肽氧化還原循環(glutathione redox cycle)

73. Mitochondrial production and disposal of superoxide

74. 抗氧化的分子 生物體也使用一些抗氧化的分子防止自由基的危害。
包括GSH、α-tocopherol (vitamin E)、ascorbic acid (vitamin C)與β-carotene。
vitamin E是一個很強的自由基清除者，是屬於phenolic antioxidants。酚是一個很有效的抗氧化劑，因為它具有共振的穩定性。

75. 圖10.22 選擇的抗氧劑

76. ATP synthase
Mitochondrial ATP synthase is an F-type ATPase. It, called Complex V, has two distinct components: F1, a peripherial membrane protein, and Fo (o denoting oligomycin-sensitive), which is integral to the membrane. F1, the first factor recognized as essential for oxidative and purified by Efraim Racker and his colleagues.
粒線體ATP synthase 是屬於F型ATP synthase，
: F1是膜週邊蛋白(1表第一個被Efraim Racker 團隊純化出的氧化因子)，Fo (O denoting oligomycin-sensitive)，是穿膜蛋白。

77. ATPase localized on the inner mitochondrial membrane catalyzes the formation of ATP from ADP and Pi, accompanied by the flow of protons from the P to the N sdie of the membrane.
ATPase位於粒線體內膜，質子的流進伴隨ATP的合成

78. What accounts for the huge difference?
ATP synthase stabilizes ATP relative to ADP + Pi by binding ATP more tightly, releasing enough energy to counterbalance the cost of making ATP. ATP合成酶與ATP結合力很強，遠大與ADP或 Pi 的結合。
Measurements of binding constants show that FoF1 binds ATP with very high affinity (Kd ≦10-12 M) and ADP with much lower affinity (Kd ≒10-5 M).
The difference in Kd corresponds to a difference of about 40 kJ/mol in binding energy, and this binding energy drives the equilibrium toward formation of the product ATP.由於結合力的不同，造成約40 kJ/mol差異，使得反應傾向ATP形成。

79. The proton gradient drives the release of ATP from the enzyme surface.

80. ATP synthase
Mitochondrial F1 has nine subunits of five different types, with the composition a3b3gde.
Each of the three b subunits has one catalytic site for ATP synthesis.
The crystallographic determination of the F1 structure by John E. Walker and colleagues revealed structural details very helpful in explaining the catalytic mechanism of the enzyme. ATP synthase 的結晶結構由John E. Walker 等解出。

81. The F1 complex
Each b subunit, near its interface with the neighboring a subunit, has a nucleotide-binding site critical to the catalytic activity.
The F1 complex具有nucleotide的結合位置於b subunits。
The single g subunit associates primarily with one of the three ab pairs, forcing each of the three b subunits into slightly different conformations, with different nucleotide-binding sites. .

82. The Fo complex
The Fo complex making up the proton pore is composed of three subunits, a, b, and c, in the proportion ab2c10-12.
The Fo complex 組合成質子通道。
Subunit c is a small (Mr 8,000), very hydrophobic polypeptide, consisting almost entirely of two transmembrane helices, with a small loop extending from the matrix side of the membrane.

83. Diagram of the FoF1 complex, deduced from biochemical and crystallographic studies

84. Diagram of the FoF1 complex
The two b subunits of Fo associate firmly with the a and b subunits of F1, holding them fixed relative to the membrane. FoF1 complex的圖
In Fo, the membrane-embedded cylinder of c subunits is attached to the shaft made up of F1 subunits g and e.

85. Binding-change model for ATP synthase

86. Chemiosmotic coupling allows nonintegral stoichiometries of O2 consumption and ATP synthesis
If 10 protons are pumped out per NADH and 4 must flow in to produce 1 ATP, the proton-based P/O ratio is 2.5 for NADH as the electron donor and 1.5 for succinate.
1NADH可產生2.5 ATP
1FADH2可產生1.5 ATP

87. Adenine nucleotide and phosphate translocases (located in the inner mitochondrial membrane)

88. Shuttle systems indirectly convey cytosolic NADH into mitochondria for oxidation
malate-asparate shuttle— producing 2.5 ATP. 肝與心臟細胞
Glycerol 3-phosphate shuttle—producing 1.5 ATP. 肌肉與腦細胞

89. Malate-asparate shuttle

90. Glycerol 3-phosphate shuttle

92. Regulation of oxidative phosphorylation
Oxidative phosphorylation is regulated by cellular energy demands. The intracellular [ADP] and the mass-action ratio [ATP]/([ADP][Pi]) are measures of a cell’s energy status.
氧化磷酸化的調節是由[ATP]/([ADP][Pi]的比例來決定。

93. Regulation of the ATP-producing pathways

95. Uncoupled mitochondria in brown fat produce heat
Most newborn mammals, including humans, have a type of adipose tissue called brown fat in which fuel oxidation serves not to produce ATP but to generate heat to keep the newborn warm.大部分哺乳動物的幼兒，其脂肪組織具有棕色脂肪。可以行脂肪氧化，非產生ATP而產熱。

96. The mitochondria of brown fat have a unique protein in their inner membrane.
Thermogenin, also called the uncoupleing protein, provides a path for protons to return to the matrix without passing through the FoF1 complex.
因為棕色脂肪粒線體膜上具有獨特的蛋白Thermogenin又稱uncoupleing protein，會破壞質子梯度。

97. Heat generation by uncoupled mitochondria

98. Mitochondrial P-450 oxygenases catalyze steroid hydroxylations
Mitochondria are the site of biosynthetic reaction that produce steroid hormones, including the sex hormones, glucocorticoids, mineralocorticoids, and vitamin D hormone.
粒線體是合成類固醇與維生素D的胞器。
These hormones are synthesized from cholesterol or a related sterol in a series of hydroxylations catalyzed by the enzymes of the cytochrome P-450 family.這些荷爾蒙是由膽固醇經一系的羥化反應而成，而催化這些反應的酵素為cytochrome P-450 家族的成員。

99. In the hydroxylation reactions, one atom of molecular oxygen is incorporated into the substrate and the second is reduced to H2O:
R-H + O2 + NADPH → R-OH + H2O + NADP+
羥化反應的方程式如上。

100. Mitochondrial P-450 oxygenases catalyze steroid hydroxylations
Cytochrome P-450 enzymes are situated in the inner mitochondrial membrane with their catalytic site exposed to the matrix.
All of P-450 enzyme have a critical heme group. Its absorption at 450 nm gives this family its name。
Cytochrome P-450酵素位於粒線體內膜，其催化的位置曝露於基質中。具有血質(heme), 因對450奈米具有強的吸收故名之。

101. The path of electron flow in the mitochondrial P-450 system is involved a flavoprotein and an iron-sulfur protein that carry electrons from NADPH to the P-450 heme.
P-450系統的電子流動路徑包含黃素蛋白、硫鐵蛋白與NADPH。

102. Mitochondria of adrenal gland, specialized for steroid synthesis

103. Path of electron flow in mitochondrial cytochrome P-450 reactions in adrenal gland

104. Another large family of P-450 enzymes
Found in the ER of hepatocytes.另一大族群則位內質網，催化反應類似於粒線體的P-450 enzymes。主要用於解毒代謝。
Catalyze reactions similar to the mitochondrial P-450 reactions.
Their substrates include a wide variety of hydrophobic compounds, many of which are xenobiotics－compounds not found in nature but synthesized industrially.

105. Hydroxylation of the hydrophobic compounds makes them more water soluble, and they can then be cleared by the kidneys and excreted in urine.
羥化不溶於水的疏水性的化合物，可增加其溶解度，有利於排出體外。

106. The role of mitochondria in apoptosis
Besides their central role in ATP synthesis, mitochondria also participate in processes associated with cellular damage and death. 除了合ATP的角色，粒線體也參與細胞損壞與死亡的過程。
Apoptosis: Programmed cell death, in which a cell brings about its own death and lysis, signaled from outside or programmed in its genes, systematically degrading its own macromolecules.細胞凋亡，是計劃性的細死亡。當細胞接受到死亡訊息，會增加粒線體外膜的通透性。有利 於cytochrome c 漏出，漏出的cytochrome c會活化caspase 9，導致細胞凋亡的啟動。

107. When a cell receives a signal for apoptosis, one consequence is an increase in the permeability of the outer mitochondrial membrane ( the opening of the permeability transition pore complex (PTPC)), allowing escape of the cytochrome c normally confined in the intermembrane space.
The released cytochrome c activates one of the proteolytic enzymes (caspase 9) responsible for protein degradation during apoptosis.

108. Role of cytochrome c in apoptosis

110. Mitochondrial genes
Mitochondria contain their own genome, a circular double-stranded DNA (mtDNA) molecule.粒線體內有一環狀的雙股螺旋的DNA。共16569 bases，無intron且內含37個基因。隨細胞分裂而分裂。只有13 genes被轉譯。絕大部分(95%以上)的粒線體蛋白是由染色體中的基因所轉譯再送至粒線體中。

111. Mitochondrial genes and mutations

112. Mutations in mitochondrial DNA accumulate throughout the life of the organism
The respiratory chain is the major producer of ROSs in cells, so mitochondrial contents, including the mitochondrial genome, suffer the greatest exposure to, and damage by ROS.
The mitochondrial DNA replication system is less effective than the nuclear system at correcting mistakes made during replication and at repairing DNA damage.
One theory of aging is that this gradual accumulation of defects with increasing age is the primary cause of many of the symptoms of aging, which include progressive weakening of skeletal and heart muscle.

113. Heteroplasmy in mitochondrial genomes

114. Different cells in the same tissue are affected to different degrees by the mitochondrial mutation
The cells from human muscle tissue are stained to make wild-type cell blue and cells with mutant cytochrome oxidase brown.

115. 染色體基因的突變導致人的疾病
染色體基因的突變known as the mitochondrial encephalomyopathies主要發生在腦與肌肉(兩者需供應大量的ATP)
這些疾病主要是遺傳自母親，因成長的胚胎的染色體是來自母親的卵。

116. 染色體基因突變的遺傳疾病 賴博氏遺傳性視覺神經症 ( Leber Hereditary Optic Neuropathy, LHON )
Myoclonic epilepsy and ragged-red fiber disease (MERRF)(肌陣攣性癲癇發作伴破碎紅纖維病變)