Mitochondria as intracellular signalling organelles. An update.

Traditionally, mitochondria are known as "the powerhouse of the cell," responsible for energy (ATP) generation (by the electron transport chain, oxidative phosphorylation, the tricarboxylic acid cycle, and fatty acid ß-oxidation), and for the regulation of several metabolic processes, including redox homeostasis, calcium signalling, and cellular apoptosis. The extensive studies conducted in the last decades portray mitochondria as multifaceted signalling organelles that ultimately command cells' survival or death. Based on current knowledge, we'll outline the mitochondrial signalling to other intracellular compartments in homeostasis and pathology-related mitochondrial stress conditions here.

Deciphering the relationship between caveolae-mediated intracellular transport and signalling events.

The caveolae-mediated transport across polarized epithelial cell barriers has been largely deciphered in the last decades and is considered the second essential intracellular transfer mechanism, after the clathrin-dependent endocytosis. The basic cell biology knowledge was supplemented recently, with the molecular mechanisms beyond caveolae generation implying the key contribution of the lipid-binding proteins (the structural protein Caveolin and the adapter protein Cavin), along with the bulb coat stabilizing molecules PACSIN-2 and Eps15 homology domain protein-2. The current attention is focused also on caveolae architecture (such as the bulb coat, the neck, the membrane funnel inside the bulb, and the associated receptors), and their specific tasks during the intracellular transport of various cargoes.

Mitochondrial-derived vesicles: Recent insights.

The generation of vesicles is a constitutive attribute of mitochondria inherited from bacterial ancestors. The physiological conditions and mild oxidative stress promote oxidation and dysfunction of certain proteins and lipids within the mitochondrial membranes; these constituents are subsequently packed as small mitochondrial-derived vesicles (MDVs) (70-150 nm in diameter) and are transported intracellularly to lysosomes and peroxisomes to be degraded. In this way, MDVs remove the damaged mitochondrial components, preserve mitochondrial structural and functional integrity and restore homeostasis.

One step forward: extracellular mitochondria transplantation.

Mitochondria play a key role in cellular energy production and contribute to cell metabolism, homeostasis, intracellular signalling and organelle's quality control, among other roles. Viable, respiratory-competent mitochondria exist also outside the cells. Such extracellular/exogenous mitochondria occur in the bloodstream, being released by platelets, activated monocytes and endothelial progenitor cells.

Mitochondrial biogenesis: An update.

In response to the energy demand triggered by developmental signals and environmental stressors, the cells launch the mitochondrial biogenesis process. This is a self-renewal route, by which new mitochondria are generated from the ones already existing. Recently, considerable progress has been made in deciphering mitochondrial biogenesis-related proteins and genes that function in health and in pathology-related circumstances.

Mitochondrial peptides-appropriate options for therapeutic exploitation.

Besides their well-known function in cellular bioenergetics, the role of mitochondria in signaling regulation of cells homeostasis and survival has been uncovered during the past few decades. Possessing an independent genome and a unique genetic code, mitochondria biosynthesize protective stress response factors, the "mitochondrial-derived peptides," import and deposit peptides within their matrix and are the target of peptides bound to bioactive agents, aiming at alleviation of pathology-related malfunction of the electron transport chain. As the rapidly evolving field of mitochondrial peptides is appropriate for therapeutic exploitation, a brief overview of the major recent findings is timely needed.

Mitochondrial networking in diabetic left ventricle cardiomyocytes.

Cardiomyocyte mitochondria preserve "the quorum sensing" attribute of their aerobic bacterial ancestors, as shown by the transient physical connectivity and communication not only with each other, but also with other intracellular organelles and with cytosol, ensuing cellular homeostasis. In this review, we present original electron microscopy evidence on mitochondrial networking within diabetic left ventricular cardiomyocytes, focusing on: (i) the inter-mitochondrial communication, allowing electrochemical signals transfer and outer membrane components or matrix proteins exchange, (ii) the interplay between mitochondria and the cardiomyocyte nucleus, nucleolus, sarcoplasmic reticulum, lysosomes, and lipid droplets viewed as attributes of mitochondrial "quality control" and "retrograde signaling function", and (iii) the crosstalk between mitochondria and cardiomyocyte cytosol, as part of the adaptive responses that allow cells survival. Confirmation of such interactions in diabetic myocardium and identification of molecules involved are ongoing, foreseeing the alleviation of heart contractile dysfunction in cardiomyopathy.