For instance, in malignant cells related to the tumor-predisposing syndrome neurofibromatosis type 1 (NF1), the hyperactivation of Ras/ERK signaling, which occurs downstream to loss of neurofibromin, dampens the expression and activity of complex I, lowering both respiration and intracellular NAD+ levels. Here, NF1 is linked to neurofibromatosis type 1.