Mitochondrial bioenergetics in different pathophysiological conditions

Mitochondria are complex intracellular organelles involved in many aspects of cellular life, with a primary role in bioenergy production via oxidative phosphorylation (OXPHOS). In this Special Issue, nine review papers were published dealing with compelling topics related to mitochondrial bioenergetics and other linked multifunctional roles of mitochondria in various pathophysiological contexts. Mitochondrial OXPHOS disorders are critical contributors involved in the pathogenesis of a broad range of human diseases directly or indirectly through a wide spectrum of signaling pathways [1]. In their review, Protasoni and Zeviani have analyzed, in detail, the structure, the assembly pathway and the organization in supercomplexes of selective components of the OXPHOS machinery, reviewing how single or isolated defects in specific mitochondrial respiratory chain proteins are linked to a variety of human disorders [2]. The authors discussed the heterogeneity and the complexity behind the still-growing group of pathologies normally identified as "mitochondrial diseases", the pathophysiology of which is still often poorly understood. Among them, primary mitochondrial diseases are associated with genetic mutations both in nuclear and mitochondrial DNA (mtDNA), affecting genes involved in every aspect of the organelle function [2]. In the energy metabolism, the mitochondrial adenine nucleotide translocator (ANT) plays the fundamental role of gatekeeper and key regulator of cellular bioenergetic flow, carrying out the reversible exchange of ADP for ATP across the inner mitochondrial membrane [3]. In their review, Atlante and Valenti focused on this mitochondrial translocator, making "A walk in the memory: from the first Functional Approach up to Its Regulatory Role of Mitochondrial Bioenergetic Flow in Health and Disease" [3]. In particular, the authors reviewed and discussed among their studies all those in which they were able to measure the functional activity of ANT in a variety of pathophysiological contests, by using an--ancient but still actual- experimental strategy allowing them to monitor continuously the transfer of energy in the form of ATP from the inside of the mitochondria to the outside, under conditions close to a biological status reflecting what really happens in the cellular microenvironment [3]. Mitochondria are highly dynamic organelles, the morphology of which is tightly linked to their functions, ongoing fusion and fission events, reshaping their morphology as well as to relocate within the cell, thus supporting critical energy power needs [4]. In addition, growing evidence established a connection between dysregulated mitochondrial dynamics and disease development and progression. In particular, defects in key components of the machinery mediating mitochondrial dynamics have shown to be linked with a wide range of pathological conditions, including metabolic, immune and neurodegenerative diseases [5]. Regarding this, a further update on the molecular mechanisms promoting mitochondrial fusion and fission in mammals has been provided by Kyriakoudi et al. [6]. The authors discussed on the emerging association of human diseases with aberrant mitochondrial dynamics, making the latter as a major culprit for disease pathogenesis and an attractive target for therapy. Neurological disorders, including neurodegenerative diseases, are collectively a major cause of death and disability worldwide. Altered mitochondrial function has been implicated in most of these diseases, but key information about how this dysfunction occurs, whether it is a cause or an effect, how it differs in different neurological conditions and how the dysfunction progresses, is lacking. Moreover, studying mitochondrial function in these disorders is di