Chemical genetics is an emerging technology for revealing the signaling networks that regulate biological phenotypes using exogenous reagents such as small organic molecules. To study neurobiology using chemical genetics, high-throughput cell and organismal assays can be created to identify compounds and proteins that regulate diverse neuronal phenotypes, such as cell viability, gene expression...

Mitophagy, the autophagic degradation of mitochondria, is an important housekeeping function in eukaryotic cells, and defects in mitophagy correlate with ageing phenomena and with several neurodegenerative disorders. A central mechanistic question regarding mitophagy is whether mitochondria are consumed en masse, or whether an active process segregates defective molecules from functional ones w...

Currently, extensive investigations are being carried out in the area of mitochondrial genomics. Mitochondrial DNA is used in many fields of science, e.g. evolutionism, phylogeography, anthropology, archaeology, forensics, medical diagnostics, veterinary medicine, molecular ecology, population genetics, and animal breeding. Mitochondrial markers, haplotypes, or haplogroups are associated with p...

................................................................................................... 10 Thesis declaration .................................................................................... 11 Acknowledgments ................................................................................... 12 General Introduction ..................................................................

For most of the past century, prehistorians have had to rely on the fossil and archaeological records in order to reconstruct the past. In the last few decades, this evidence has been substantially supplemented from classical human genetics. More recently, phylogenetic analyses of DNA sequences that incorporate geographical information have provided a high-resolution tool for the investigation ...

Mitochondrial diseases are a group of disorders due to a mitochondrial respiratory chain deficiency. They may depend on mitochondrial genome (mtDNA-related disorders) as well as on a nuclear genome defect (nDNA-related disorders). mtDNA-related disorders encompass an increasing number of clinical pictures associated with more than 250 different provisional or confirmed pathogenic changes in mtD...

Mitochondria cannot be produced de novo by the cell, but are inherited across generations. Their peculiar genetics (multiple genomes per cell, no meiosis, replication independent from cell cycle, high mutation rate) and the possible exposition to Reactive Oxygen Species (ROS) are predicted to produce a fast accumulation of deleterious mutations, a phenomenon known as Müller’s ratchet. Nonethele...

This review addresses the mechanisms by which mitochondrial structure and function are regulated, with a focus on vertebrate muscle. We consider the adaptive remodeling that arises during physiological transitions such as differentiation, development, and contractile activity. Parallels are drawn between such phenotypic changes and the pattern of change arising over evolutionary time, as sugges...