The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

Recommendations

Info

An Introduction to Mitochondria Fig. 2.1. The endosymbiotic theory of the origin of mitochondria. 2.2. Mitochondrial Location and Structure 2.2.1. Location As explained in the previous section, mitochondria are components of cells: subcellular organelles. Different cell types contain different numbers of them; the extremes are that red blood cells (erythrocytes) contain none and egg cells (ova) contain about 100,000. Most human cells contain between a few hundred and a few thousand. All our cells (except platelets and, again, red blood cells) have a nucleus, which is the compartment containing our chromosomes. Mitochondria are never found in the nucleus, only in the rest of the cell (the cytoplasm). The cytoplasm is also sometimes called the cytosol; strictly, the cytoplasm is everything inside the cell except the nucleus (so including 7
8 The Mitochondrial Free Radical Theory of Aging mitochondria and other organelles), whereas “cytosol” denotes the cytoplasm minus the organelles. Mitochondria are distributed throughout the cytoplasm. Even in very long and thin cells, such as nerves, there are mitochondria all the way to the end—sometimes feet from the nucleus. They occupy a substantial fraction of the cell volume: about 1/5 in liver cells, for example. The components of a mitochondrion which will feature in this book are shown in Figure 2.2. 2.2.2. Macroscopic Structure “Macroscopic” in this context is relative—mitochondria are typically only a few hundred nanometres long. In this context, “macroscopic” only means “at least an order of magnitude bigger than a protein.” A mitochondrion, like all organelles, is essentially a scrap of water encased in a membrane. Unlike most organelles, though, that membrane is itself encased in another membrane. The two membranes differ in many ways. The surface area of the inner membrane is much larger than is needed to contain the material inside the mitochondrion, but is intricately folded; the folds are called cristae. The outer membrane is not folded. The outer membrane has large holes (pores, ringed by a protein called, helpfully, porin) through which small molecules—though not most proteins—can easily pass; the inner membrane, on the other hand, is impermeable to most molecules (especially charged ones). The space enclosed by the inner membrane is called the mitochondrial matrix. The space between the inner and outer mitochondrial membranes is just called the mitochondrial intermembrane space. The membranes are both composed of the same types of molecule as all other membranes: phospholipids and cholesterol. There are some peculiarities regarding which phospholipids are present: for example, a diphospholipid called cardiolipin (see Fig. 4.1 for structure) is present in large amounts in the inner membrane, whereas it is almost absent anywhere else in the cell. 9 Conversely, cholesterol is hardly present at all in the inner mitochondrial membrane (except in the adrenal cortex, where it is metabolised to pregnenolone) 10a but is plentiful elsewhere. 9 The two membranes are not completely separate: they come together at a few places called contact sites (whose absence from Figure 2.2 will be explained later). The intermembrane space contains only a few proteins; some are involved in transport of proteins into mitochondria (see Section 2.4.3). Apart from those, the only one that will concern us is cytochrome c, which has a crucial role in mitochondrial function. The outer membrane contains some proteins too, apart from porin and some other protein-transport proteins, but none of them will feature here. The inner membrane and the matrix, on the other hand, each contain many molecules whose roles are relevant to the mitochondrial free radical theory of aging. 2.2.3. Composition of the Mitochondrial Matrix The description of the mitochondrial matrix as “a scrap of water” is not in fact terribly accurate, because a fantastically high concentration of other material is suspended in it. It has been estimated that fully half the mass of the matrix is protein. 10b These proteins are mostly enzymes: catalysts of chemical reactions that are involved in mitochondrial function. In all, there are a few hundred different ones. The matrix also contains smaller molecules, many of which are substrates or cofactors of these enzymes (that is, participants in the reactions which they catalyse). Finally, it also contains a small
Page 1 and 2: COMPANY de Grey The Mitochondrial F
Page 3 and 4: ISBN: 1-57059-564-X MOLECULAR BIOLO
Page 5 and 6: 7. The Status of Gerontological The
Page 7 and 8: 17. Conclusion: The Role of the Ger
Page 9 and 10: I cannot overstate my profound grat
Page 11 and 12: CHAPTER 1 Introduction 1.1. What Is
Page 13 and 14: Introduction Some may feel that all
Page 15: 6 The Mitochondrial Free Radical Th
Page 19 and 20: 10 The Mitochondrial Free Radical T
Page 27 and 28: 18 Fig. 2.7. The respiratory chain.
Page 33 and 34: 24 Fig. 2.9. Types of protein impor
Page 35 and 36: 26 Fig. 2.10. Why the DNA bases pai
Page 43 and 44: CHAPTER 3 An Introduction to Free R
Page 45 and 46: An Introduction to Free Radicals Ta
Page 51 and 52: An Introduction to Free Radicals Fi
Page 53 and 54: An Introduction to Free Radicals Re
Page 67 and 68:
60 The Mitochondrial Free Radical T
Page 69 and 70:
62 The Mitochondrial Free Radical T
Page 71 and 72:
CHAPTER 6 History of the Mitochondr
Page 73 and 74:
History of the Mitochondrial Free R
Page 75 and 76:
Page 77 and 78:
Page 79 and 80:
Page 81 and 82:
Page 83 and 84:
Page 85 and 86:
Page 87 and 88:
Page 89 and 90:
Page 91 and 92:
CHAPTER 7 The Status of Gerontologi
Page 93 and 94:
The Status of Gerontological Theory
Page 95 and 96:
The Status of Gerontological Theory
Page 97 and 98:
CHAPTER 8 The Search for How Mutant
Page 99 and 100:
The Search for How Mutant mtDNA is
Page 101 and 102:
Page 103 and 104:
Page 105 and 106:
Page 107 and 108:
CHAPTER 9 The Search for How So Few
Page 109 and 110:
The Search for How So Few Anaerobic
Page 111 and 112:
Page 113 and 114:
Page 115 and 116:
Page 117 and 118:
Page 119 and 120:
Page 121 and 122:
CHAPTER 10 Frequently-Asked Questio
Page 123 and 124:
Frequently-Asked Questions The effe
Page 125 and 126:
Frequently-Asked Questions Table 10
Page 127 and 128:
Frequently-Asked Questions through
Page 129 and 130:
Frequently-Asked Questions has been
Page 131 and 132:
Frequently-Asked Questions SOS, sin
Page 133 and 134:
Frequently-Asked Questions for almo
Page 135 and 136:
Frequently-Asked Questions Fig. 10.
Page 137 and 138:
Frequently-Asked Questions Fig. 10.
Page 139 and 140:
Frequently-Asked Questions of elect
Page 141 and 142:
Frequently-Asked Questions Referenc
Page 143 and 144:
Frequently-Asked Questions 45. Clay
Page 145 and 146:
CHAPTER 11 A Challenge from Textboo
Page 147 and 148:
A Challenge from Textbook Bioenerge
Page 149 and 150:
Page 151 and 152:
Page 153 and 154:
Page 155 and 156:
Page 157 and 158:
Page 159 and 160:
Page 161 and 162:
Page 163 and 164:
Page 165 and 166:
160 The Mitochondrial Free Radical
Page 167 and 168:
Page 169 and 170:
Page 171 and 172:
Page 173 and 174:
Page 175 and 176:
Page 177 and 178:
CHAPTER 14 Ablation of Anaerobic Ce
Page 179 and 180:
Ablation of Anaerobic Cells: Techni
Page 181 and 182:
CHAPTER 15 Transgenic Copies of mtD
Page 183 and 184:
Transgenic Copies of mtDNA: Techniq
Page 185 and 186:
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
Page 193 and 194:
CHAPTER 16 Prospective Impact on th
Page 195 and 196:
Prospective Impact on the Healthy H
Page 197 and 198:
Prospective Impact on the Healthy H
Page 199 and 200:
Page 201 and 202:
Page 203 and 204:
Index Symbols “~”, 19 A Acetald
Page 205 and 206:
Index Copper 35, 107 see also trans
Page 207 and 208:
Index Heart comparison to man-made
Page 209 and 210:
Index genetic code 23, 115-118, 177
Page 211 and 212:
Index Perhydroxyl radical 41, 122,
Page 213 and 214:
Index protonation see protonation (
Page 215:
MOLECULAR BIOLOGY INTELLIGENCE UNIT
show all

The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

Create successful ePaper yourself

Delete template?

Save as template?