Abstract
Oxidative stress (OS) and mitochondrial dysfunction (MDF) occur in a number of disorders, and several clinical studies have attempted to counteract OS and MDF by providing adjuvant treatments against disease progression. The present review is aimed at focusing on two apparently distant diseases, namely type 2 diabetes (T2D) and a rare genetic disease, Fanconi anemia (FA). The pathogenetic links between T2D and FA include the high T2D prevalence among FA patients and the recognized evidence for OS and MDF in both disorders. This latter phenotypic/pathogenetic feature—namely MDF—may be regarded as a mechanistic ground both accounting for the clinical outcomes in both diseases, and as a premise to clinical studies aimed at counteracting MDF. In the case for T2D, the working hypothesis is raised of evaluating any in vivo decrease of mitochondrial cofactors, or mitochondrial nutrients (MNs) such as α-lipoic acid, coenzyme Q10, and l-carnitine, with possibly combined MN-based treatments. As for FA, the established knowledge of MDF, as yet only obtained from in vitro or molecular studies, prompts the requirement to ascertain in vivo MDF, and to design clinical studies aimed at utilizing MNs toward mitigating or delaying FA’s clinical progression. Altogether, this paper may contribute to building hypotheses for clinical studies in a number of OS/MDF-related diseases.
Highlights
Redox and mitochondrial anomalies are recognized—since the pioneering report by Luft (1994) [1]on “mitochondrial medicine”—in an extensive number of disorders that are afferent to several medical disciplines [2,3,4,5], including diabetes, aging, and genetic, neurologic and neuropsychiatric, and cardio-vascular diseases
After the pioneering report by Mukhopadhyay et al in 2006 [107], it became clear that a Fanconi anemia (FA) gene product (FA-G) was associated with mitochondrial dysfunction (MDF), opening the way toward the assumption that FA proteins may be related to the control of mitochondrial activity [108,109,110]
The amino acid derivative carnitine (CARN) is primarily synthesized in the liver in its L-form from lysine and methionine and transported via the bloodstream to cardiac and skeletal muscle [131]. It is required for mitochondrial fatty acid β-oxidation and transport of long-chain fatty acids across the inner membrane of the mitochondria, in the form of acyl-carnitine, where they can be metabolized for energy
Summary
Redox and mitochondrial anomalies are recognized—since the pioneering report by Luft (1994) [1]. (coQ10), and carnitine (CARN), termed mitochondrial nutrients (MNs) [8] These are involved in three basic mitochondrial functions, namely the Krebs cycle (ALA), the electron transport chain (coQ10), and acyl transfer (CARN), as recognized since the early report by Palade in 1964 [9]. Among the extensive number of OS/MDF-related disorders [2], the present review is focused on two apparently unrelated diseases, such as a pandemic disease as T2D and a rare genetic disease as FA. These may be seen as two paradigms both offering mechanistic insights of the two disorders and providing working hypotheses toward adjuvant treatments of these and other OS/MDF-related disorders
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