ATP5IF1 (ATP Synthase Inhibitory Factor Subunit 1)

Secondary structure analyses based on chemical shifts and short-range NOE patterns indicate the N-terminal half of the 81-residue IF1 is intrinsically disordered, while the C-terminal half adopts a continuous α-helix. The chemical shift assignments for human IF1 provide a foundation for future mechanistic structure-function studies and NMR-based drug screening.

G protein subunit alpha Z (GNAZ), a miR-20a-3p target protein, can promote VM by phosphorylating components of the ERK pathway. Collectively, these results delineate a novel IF1/ESR1/miR-20a-3p/GNAZ axis in HCC VM and metastasis, providing potential therapeutic targets.

Secondary structure analyses based on chemical shifts and short-range NOE patterns indicate the N-terminal half of the 81-residue IF1 is intrinsically disordered, while the C-terminal half adopts a continuous α-helix. The chemical shift assignments for human IF1 provide a foundation for future mechanistic structure-function studies and NMR-based drug screening.

The impact of glycolytic inhibition by 2-Deoxy-D-glucose (2-DG) on CAR-NK92 antitumor capacity was examined...Conclusion ATPIF1 regulates the antitumor activity of CAR-NK92 cells through modulating glycolytic metabolism. Overexpression of ATPIF1 can enhance the antitumor efficacy of CAR-NK92 cells.

Sorted hyperpolarized WT and ovarian cancer cells naturally depleted of IF1 also showed phospholipid remodeling, indicating this as an adaptation to mitochondrial hyperpolarization. These data provide a new framework for how mitochondria can impact epigenetics and cellular biology to influence health outcomes, including through chemical exposures and in disease states.

Knockdown of ATP5IF1 conferred venetoclax resistance, while ATP5IF1 overexpression impaired F1-ATPase activity and heightened sensitivity to venetoclax. These data identify matrix ATP consumption as a cancer cell-intrinsic bioenergetic vulnerability actionable in the context of BCL-2 targeted chemotherapy.

Importantly, macrophages, not Schwann cells, are identified as key contributors to the delayed Wallerian degeneration in ATPIF1 knockout mice, and affect the overall outcome of peripheral nerve regeneration. These results shed light on the translational potential of ATPIF1 for improving peripheral nerve regeneration.

Moreover, we emphasize that IF1 is phosphorylated in vivo in its S39 by the c-AMP-dependent PKA activity of mitochondria to render an inactive inhibitor that is unable to interact with the enzyme, thus triggering the activation of ATP synthase. Overall, we discuss and challenge the results that argue against the role of IF1 as in vivo inhibitor of mitochondrial ATP synthase and stress that IF1 cannot be regarded solely as a pro-oncogenic protein because in some prevalent carcinomas, it prevents metastatic disease.

Collectively, our findings revealed that HSK3486 induces oxidative stress, resulting in colorectal cancer cell apoptosis, making it a potential candidate therapeutic strategy for colorectal cancer.

SUM159 cells incubated with TR57 up to 72 h retained the level of proteins facilitating the ATP transfer across the mitochondrial membranes: VDAC1 expression was not affected, while expression of ANT-1/2 and APC2 increased by 20% and 40%, respectively. Thus, our results suggest that although TR-57 treatment leads to complete inhibition of respiratory chain activity of SUM159 cells, hydrolysis of cytoplasmic ATP by reversal activity of FF-ATPase supports mitochondrial polarization.

Genes in mitochondrial complexes I (NDUFA12 and NDUFB6) and V (ATP5PB and ATP5IF1) were overexpressed and were associated with poorer survival, and the results were independently validated in the TARGET AML cohort. In conclusion, concurrent WT1 or DNMT3A mutations and a dysregulated immune and metabolic state were correlated with poor survival in patients with CEBPA, and upfront allogeneic transplantation may be indicated for better long-term disease control.

In addition, we review recent findings stressing that mitochondria metabolism is the primary altered target in lung adenocarcinomas and that the ATP synthase/IF1 axis of OXPHOS is included in the most significant signature of metastatic disease. Finally, we stress that targeting mitochondrial OXPHOS in pre-clinical mouse models affords a most effective therapeutic strategy in cancer treatment.