DJ-1 promotes energy balance by regulating both mitochondrial and autophagic homeostasis

Molecular and Physiological Determinants of Amyotrophic Lateral Sclerosis: What the DJ-1 Protein Teaches Us

“…At least three independent studies observed an association between DJ-1 deficiency and decreased ATP levels, either in cell or D. melanogaster models [53,59,66], probably due to mitochondrial complex I impairment [53]. In contrast with these studies, despite a decreased complex-I-linked oxygen consumption rate, we were unable to detect any variation in ATP and/or ADP levels in DJ-1 knock-out flies under either fed or starved conditions [28]. However, very interestingly, we observed that DJ-1-deficient flies exposed to starvation showed premature mortality, suggesting that while under fed conditions, the activation of some compensatory mechanisms, such as glycolysis, gluconeogenesis, and/or fatty acid oxidation, may contribute to the maintenance of ATP levels, they fail under prolonged starvation [28].…”

“…As aforementioned, the most widely accepted function of DJ-1 is its protective role against excessive ROS levels. Accordingly, the overexpression of DJ-1 results in neuronal cytoprotection against oxidative damage, whereas DJ-1 deficiency leads to an increase in oxidative-stress-induced cell death, both in cell cultures and animal models [28][29][30][31][32][33][34][35][36]. In this regard, it has been suggested that DJ-1 may sense the cellular redox state through a highly conserved cysteine residue localized at position 106, contributing to the regulation of redox homeostasis [37].…”

“…Collectively, these results show that DJ-1 participates in the regulation of the cellular redox state and in the maintenance of mitochondrial homeostasis, supporting the already Besides the regulation of signaling cascades, several studies have demonstrated the role of DJ-1 in the maintenance of mitochondrial homeostasis (Figure 1). Accordingly, DJ-1 deficiency is associated with several mitochondrial morphological and functional phenotypes, including mitochondrial fragmentation, reduced calcium uptake, impaired respiration, and altered membrane potential [28,[52][53][54][55][56][57]. Moreover, DJ-1 has been described to participate in the process of mitochondrial quality control, being involved in the Parkin/PINK1-mediated mitophagy [54,[58][59][60], although conflicting results exist in the literature concerning the molecular mechanisms of such involvement.…”

“…Nonetheless, the most corroborated and accepted physiological role of DJ-1 is its participation in the cellular antioxidant response. In this frame, as described below, DJ-1 participates in mitochondria homeostasis and in the preservation of reactive oxygen species (ROS) physiological levels [28]. While DJ-1 functions seem to be redundant, they could acquire relevance under stressful conditions, and the DJ-1 multimodal response to different sources of stress might represent the way DJ-1 exerts its neuronal protection role.…”

Involvement of DJ-1 in the pathogenesis of intervertebral disc degeneration via hexokinase 2-mediated mitophagy

“…DJ-1 is a multifunctional protein encoded by the PARK7 gene and is involved in cellular processes such as intracellular antioxidant defense 19 , 20 , transcriptional regulation 21 , and autophagy regulation 22 . Although DJ-1 is widely expressed and plays an important role in a variety of cells, our understanding of the function of DJ-1 is limited.…”