The less complex DNA replication and repair systems in mitochondria mean that accidents are corrected less efficiently. This results in a 100-fold higher occurrence of deletions and point mutations than in nuclear DNA. Mathematical modeling suggests that most of these mutations and lesions are acquired in childhood or early adult life, and then proliferate by clonal expansion in later life. Due to mitotic segregation, some cells will accumulate higher levels of faulty mitochondrial DNA than others. Above some threshold, serious deficiencies in respiratory-chain function will develop, producing cells that are senescent. In many organs of the human body, senescent cells with high levels of mitochondrial DNA damage are intermingled with normal cells, resulting in a mosaic of cells with and without respiratory-chain deficiency.
The main role of mitochondrial fusion in cellular physiology is most likely to ensure an even distribution of mitochondrial DNA throughout the mitochondrial reticulum, and to prevent the accumulation of damaged DNA in one part of the network. When the fusion machinery is defective, DNA is lost from a subset of the mitochondria in the cell. Loss of mitochondrial DNA leads to a loss of respiratory-chain function, and it can cause disease.
All of the considerations just discussed have suggested to some scientists that changes in our mitochondria are major contributors to human aging. However, there are many other processes that tend to go wrong as cells and tissues age, as one might expect given the incredible complexity of human cell biology. Despite intensive research, the issue remains unresolved.
Why Do Mitochondria and Chloroplasts Maintain a Costly Separate System for DNa transcription and translation?
Why do mitochondria and chloroplasts require their own separate genetic systems, when other organelles that share the same cytoplasm, such as peroxisomes and lysosomes, do not? The question is not trivial, because maintaining a separate genetic system is costly: more than 90 proteins—including many ribosomal proteins, aminoacyl-tRNA synthetases, DNA polymerase, RNA polymerase, and RNA-processing and RNA-modifying enzymes—must be encoded by nuclear genes specifically for this purpose. Moreover, as we have seen, the mitochondrial genetic system entails the risk of aging and disease.
A possible reason for maintaining this costly and potentially hazardous arrangement is the highly hydrophobic nature of the nonribosomal proteins encoded by organelle genes. This may make their production in and import from the cytoplasm simply too difficult and energy-consuming. It is also possible that the evolution (and eventual elimination) of the organellar genetic systems is still ongoing, but for now there is no alternative for the cell than to maintain separate genetic systems for its nuclear, mitochondrial, and chloroplast genes.
Mitochondria are organelles that allow eukaryotes to carry out oxidative phosphorylation, while chloroplasts are organelles that allow plants to carry out photosynthesis. Presumably as a result of their prokaryotic origins, each organelle maintains and reproduces itself in a highly coordinated process that requires the contribution of two separate genetic systems—one in the organelle and the other in the cell nucleus. The vast majority of the proteins in these organelles are encoded by nuclear DNA, synthesized in the cytosol, and then imported individually into the organelle. Other organelle proteins, as well as organelle ribosomal and transfer RNAs, are encoded by the organelle DNA; these are synthesized in the organelle itself.