The Structure and Functions of Mitochondria
In eukaryotic cells, mitochondria use aerobic oxidation to generate ATP. These multifunctional organelles are also responsible for many other key activities (see Table 12-1), including biosynthesis and metabolism of a wide variety of small molecules and regulated cell death.
The mitochondrion has two distinct membranes (outer and inner) and two distinct subcompartments (the intermembrane space between the two membranes, and the matrix surrounded by the inner membrane) (see Figure 12-6). Aerobic oxidation occurs in the mitochondrial matrix and on the inner mitochondrial membrane.
The inner mitochondrial membrane is a single continuous membrane with three compositionally, structurally, and functionally distinct domains: boundary membrane, cristae, and crista junctions.
There are at least 1100 proteins associated with mammalian mitochondria, most of which are encoded by nuclear genes. The mechanisms by which proteins enter the mitochondria are described in Chapter 13.
Mitochondria and chloroplasts most likely evolved from bacteria that formed a symbiotic relationship with ancestral cells containing a eukaryotic nucleus (see Figure 12-7).
Most of the genes originally within mitochondria and chloroplasts were either lost because their functions were redundant with nuclear genes or moved to the nuclear genome over evolutionary time, leaving different gene sets in the organelle DNAs of different organisms (see Figure 12-10).
Because most mtDNA is inherited from egg cells rather than sperm, mutations in mtDNA exhibit a maternal cytoplasmic pattern of inheritance. Similarly, chloroplast DNA is exclusively inherited from the maternal parent.
Animal mtDNAs are circular molecules, reflecting their probable bacterial origin. Plant mtDNAs and chloroplast DNAs are generally longer than mtDNAs from other eukaryotes, largely because they contain more noncoding regions and repetitive sequences.
Mitochondrial DNA (mtDNA) in the mitochondrial matrix and chloroplast DNAs encode rRNAs and some of the proteins involved in mitochondrial or photosynthetic electron transport and ATP synthesis. Mammalian mtDNA encodes only 13 proteins. Most animal mtDNAs and chloroplast DNAs also encode the tRNAs necessary to translate the organelle mRNAs.
Mitochondrial ribosomes resemble bacterial ribosomes in their structure and in their sensitivity to drugs such as chloramphenicol (sensitive) and cycloheximide (resistant).
The genetic code of animal and fungal mtDNA differs slightly from that of bacterial and nuclear genomes and varies among different animals and fungi (see Table 12-2). In contrast, plant mtDNAs appear to conform to the standard genetic code.
Several human neuromuscular disorders result from mutations in mtDNA. Patients generally have a mixture of wild-
Mitochondria are dynamic organelles, undergoing fusion and fission reactions that are regulated by the state of the cell. In many cells, the fused mitochondria form a large, interconnected branched tubular network. A family of GTPases mediate mitochondrial membrane fusion and fission (see Figure 12-12). Mutations in the genes encoding some of these GTPases cause human diseases.
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Mitochondrial fission and fusion are thought to play roles in maintaining a relatively homogeneous population of mitochondria, distributing mitochondria among the daughter cells during cell division, and establishing a system of quality control to permit culling of defective mitochondria from healthy mitochondria. Defective mitochondria or segments of mitochondria are destroyed by a processed called mitophagy.
Two proteins that can mediate mitophagy, PINK1 and Parkin, are encoded by genes that, when mutated, are responsible for hereditary early-
Mitochondria-
The MAM/mitochondrial interface significantly influences many cellular functions, including mitochondrial shape and dynamics (see Table 12-1).
The MAM/mitochondrial interface plays a key role in moving calcium from the ER into the mitochondria. Calcium influx into mitochondria from MAMs can stimulate ATP synthesis and, in the context of mitochondrial calcium overload, initiates a program of regulated cell death.