Dear Colleagues,

Since the discovery of cytochrome c release from mitochondria as a key step in the initiation of apoptotic cell death more than 20 years ago, mitochondrial research has experienced a tremendous boost. Researchers have been gathering a growing wealth of knowledge recognizing the central role of these organelles in the maintenance of eukaryotic cell homeostasis. This role is not restricted to the generation of intermediary metabolites and the ATP production through the tricarboxylic acid cycle and oxidative phosphorylation. Not only can mitochondria synthesize fundamental molecules, such as heme and iron-sulfur clusters, but they are also major sites of amino acid, nucleotide, and fatty acid metabolism and can receive, integrate, and relay intracellular signals. Mitochondrial biogenesis and functions are under tight nuclear control, through the so-called anterograde regulation of gene expression. This involves signaling pathways that coordinate gene transcription to tune finely metabolic requirements with nutritional and environmental cues. On the other hand, environmental changes trigger intracellular stress responses, which may disturb mitochondrial structure and/or function. To maintain cell homeostasis, damaged mitochondria relay signals through retrograde, instead of to anterograde, communication pathways that drive specific nuclear gene transcription patterns in response to stress. Recent advances, made primarily in budding yeast, have provided novel insights into the existence of distinct microdomains between intracellular organelles, known as membrane contact sites, that coordinate diverse activities, including mitochondrial dynamics and cell stress signaling pathways. Last but not least, it is becoming increasingly clear that mitochondrial and cytosolic proteostasis are intimately related.

In view of this and with the discovery of pathogenic mitochondrial DNA defects in the 1980s, mitochondrial dysfunction is now recognized as a common factor underlying many pathological conditions. Many of these advancements would not have been possible without the model organism Saccharomyces cerevisiae and human cell lines. This Special Issue is meant as a forum to present and discuss, in the form of research or review articles, the achievements and perspectives in the research on the multiple pathways of crosstalk between mitochondria and other cell organelles and components. At the leading edge of cell biology research, the results of these studies will lay the basis for the elucidation of mitochondrial physiology at a systems biology level.

Prof. Dr. Sergio Giannattasio
Prof. Dr. Paolo Pinton
Dr. Maša Ždralević
Guest Editors

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• Mitochondria
• OXPHOS
• mtDNA
• Energy metabolism
• ROS
• Interorganelle communication
• Proteostasis
• Mitochondrial dynamics
• Contact sites
• Yeast
• Human cell lines