The apoptosis‐inducing factor family: Moonlighting proteins in the crosstalk between mitochondria and nuclei

Novo, Nerea; Ferreira, Patricia; Medina, Milagros

doi:10.1002/iub.2390

Cited by 38 publications

(26 citation statements)

References 92 publications

(156 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its capacity to trigger cell death is controlled in part by its association with other proteins including HSP70 and cyclophilin A ( Candé et al 2004 ). The protein contains multiple conserved domains including two FAD domains and an NADH binding domain, and its function is controlled in part by redox-dependent conformational changes ( Herrmann and Riemer 2020 ; Novo et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Severe multisystem pathology, metabolic acidosis, mitochondrial dysfunction, and early death associated with an X-linked AIFM1 variant

Moss

May

Flanagan-Steet

et al. 2021

Cold Spring Harb Mol Case Stud

View full text Add to dashboard Cite

Variants in the X-linked gene AIFM1 (apoptosis-inducing factor mitochondria-associated 1) are associated with a highly variable clinical presentation that encompasses motor neuropathy, ataxia, encephalopathies, deafness, and cognitive impairment. AIFM1 encodes a mitochondrial flavin adenine dinucleotide (FAD)-dependent nicotinamide adenine dinucleotide (NADH) oxidoreductase, with roles in the regulation of respiratory complex assembly and function, production of reactive oxygen species, and the coordination of a caspase-independent type of apoptosis known as parthanatos. In this report, we describe a missense AIFM1 variant (absent in reference population databases; c.506C > T, p.Pro169Leu) identified in the proband and sibling of a family with three affected males. The proband, his brother, and their maternal uncle all exhibited severe multisystem pathology, metabolic acidosis, and early demise. Metabolic testing on the proband revealed normal activity of the pyruvate dehydrogenase complex in skin fibroblasts. Absent or partial deficiency of cytochrome c oxidase was found in muscle fibers, however, supporting a Complex IV mitochondrial deficiency. Functional studies carried out on fibroblasts from the proband demonstrated reduced steady state levels of the AIFM1 protein, decreased Complex I subunit abundance, elevated sensitivity to the apoptosis inducer staurosporine, and increased nuclear condensation when grown in galactose-containing media. The reduced abundance of AIFM1 in the patient cells could not be stabilized with riboflavin or protease inhibitor treatment. Together, these findings suggest that the normal function of the AIFM1 gene product within mitochondria, and its response to apoptotic stimuli, are impaired by this variant, likely accounting for the severity of the phenotype seen in these patients. These findings also imply tissue-specific effects of this variant on different mitochondrial complexes. This study expands the genetic and phenotypic spectrum associated with AIFM1 variants, with the combination of exome sequencing and functional studies allowing a diagnosis to finally be confirmed for this family.

show abstract

Section: Introductionmentioning

confidence: 99%

Severe multisystem pathology, metabolic acidosis, mitochondrial dysfunction, and early death associated with an X-linked AIFM1 variant

Moss

May

Flanagan-Steet

et al. 2021

Cold Spring Harb Mol Case Stud

View full text Add to dashboard Cite

show abstract

“…The interstitial connective tissue of mammalian testes is composed of different ingredients,such as blood capillaries,lymphoid vessels and Leydig cells.Leydig cells in testicular sections play crucial roles in male development and the maintenance of reproductive functions [23].We have demonstrated that the swelling of mitochondria in Leydig cells was related to oxidative stress in cryptorchid yaks [24]. Novo et al [25] revealed that oxidative stress mediates mitochondrial dysfunction and programmed cell death.In the present study,the villus protrusions of Leydig cells were not obvious and with swelling mitochondria and indistinct reticulum crowding in the cytoplasm of Leydig cells in cryptorchidism.A previous study focused on the similarities between aging-associated and cancer-associated oxidative stress and mitochondrial dysfunction as their common phenotype [26].In our study,the pathological changes of cryptorchidism in camel should be closely related to the decrease in oxidative capacity of swollen mitochondria in Leydig cells.…”

Section: Discussionmentioning

confidence: 99%

Expression of the NSE, SP, NFH and DβH in Normal and Cryptorchid Testes of Bactrian Camel

Yuan

Yang

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Neuroendocrine substances play important roles in regulating the normal physiological functions of testicles.The purpose of this study is to explore the localization and effects of four neuroendocrine markers(NSE, SP, NFH and DβH) in normal and cryptorchid testes of Bactrian camels.Methods: The cryptorchid testes were located in the abdominal cavity and were collected by orchiectomy. Fresh testes tissues were processed into small pieces and then divided into three samples. One sample was frozen in liquid nitrogen for western blotting hybridization reaction, while the other sample was fixed with 4% paraformaldehyde solution for histochemical analysis, and the third fixed in glutaraldehyde for transmission electron microscopy observation.Results: The results showed that cryptorchidism caused a reduction in layers of spermatogenic epithelium and decreased glycogen positivity in the basement membrane.The ultrastructure revealed that macrophages were always found around the Leydig cells, which were crowded with swelling mitochondria in cryptorchidism. Expression of NSE in the Leydig cells of cryptorchidism was significantly weakened compared to that in the normal group(p<0.01). We found that SP was always distributed along the nerve fibers in normal testes and was expressed in the Leydig cells of cryptorchidism. However, expression of NFH in the cryptorchidic tissue was strongly positive in spermatogenic epithelium, with limited expression in Leydig cells and no expression in peritubular myoid cells. Therefore, expression of DβH in the Sertoli cells was comparatively strong in both the normal and cryptorchidism groups.NFH and DβH expression was significantly increased in the cryptorchidism group compared with the nomal group(p<0.01).Conclusions: These findings indicated that the underdeveloped seminiferous epithelium and pathological changes in cryptorchid tissue in Bactrian camels were potentially related to a disorder in glycoprotein metabolism.Our results suggest that NSE and SP could helpful to judge the pathological changes of cryptorchidism. The present study provides the first evidence at the protein level for the existence of NFH and DβH in Sertoli and Leydig cells in Bactrian camel cryptorchidism and provides a more in-depth understanding of neuroendocrine regulation is crucial for animal cryptorchidism.

show abstract

“…An interesting bidirectional relationship exists between the mitochondria and the nucleus [ 9 ]. Following nuclear DNA damage promoted by different inducers (e.g., ultraviolet light, DNA-damaging drugs, etc.…”

Section: Introductionmentioning

confidence: 99%

Redox Imbalance and Mitochondrial Release of Apoptogenic Factors at the Forefront of the Antitumor Action of Mango Peel Extract

et al. 2021

View full text Add to dashboard Cite

Today, an improved understanding of cancer cell response to cellular stress has become more necessary. Indeed, targeting the intracellular pro-oxidant/antioxidant balance triggering the tumor commitment to cell demise could represent an advantageous strategy to develop cancer-tailored therapies. In this scenario, the present study shows how the peel extract of mango—a tropical fruit rich in phytochemicals with nutraceutical properties—can affect the cell viability of three colon cancer cell lines (HT29, Caco-2 and HCT116), inducing an imbalance of cellular redox responses. By using hydro-alcoholic mango peel extract (MPE), we observed a consistent decline in thiol group content, which was accompanied by upregulation of MnSOD—a mitochondrial scavenger enzyme that modulates the cellular response against oxidative damage. Such an effect was the consequence of an early production of mitochondrial superoxide anions that appeared after just 30 min of exposure of colon cancer cells to MPE. The effect was accompanied by mitochondrial injury, consisting of the dissipation of mitochondrial membrane potential and a decrease in the level of proteins localized in the mitochondrial membrane—such as voltage-dependent anion-selective channel (VDAC1), mitofilin, and some members of Bcl-2 family proteins (Mcl-1, Bcl-2 and Bcl-XL)—with the mitochondrial release of apoptogenic factors (cytochrome C and AIF). The analysis of the cytotoxic effects exerted by the different constituents of MPE (gallic acid, mangiferin, citric acid, quinic acid, pentagalloyl glucose, and methyl gallate) allowed us to identify those phytochemicals responsible for the observed anticancer effects, sustaining their future employment as chemopreventive or therapeutic agents.

show abstract

The apoptosis‐inducing factor family: Moonlighting proteins in the crosstalk between mitochondria and nuclei

Cited by 38 publications

References 92 publications

Severe multisystem pathology, metabolic acidosis, mitochondrial dysfunction, and early death associated with an X-linked AIFM1 variant

Severe multisystem pathology, metabolic acidosis, mitochondrial dysfunction, and early death associated with an X-linked AIFM1 variant

Expression of the NSE, SP, NFH and DβH in Normal and Cryptorchid Testes of Bactrian Camel

Redox Imbalance and Mitochondrial Release of Apoptogenic Factors at the Forefront of the Antitumor Action of Mango Peel Extract

Contact Info

Product

Resources

About