Nicotinamide-induced Mitophagy

Abstract

Background: Nicotinamide treatment decreases mitochondrial content and helps cells maintain high mitochondrial quality. Results: Metabolically enhanced NAD ϩ /NADH ratio and chemically induced SIRT1 activation similarly decreased mitochon-

New method to assess mitophagy flux by flow cytometry

“…We first demonstrated that NAM induces mitophagy even at short incubation times, in agreement with previously findings in long-term cultures of human primary fibroblasts. 26 However, these effects may be cell type-dependent, as NAM did not induce mitophagic flux at longer incubation times, nor in embryonic mouse retinas (data not shown). We also tested the effects of phenanthroline, which has been proposed to induce mitophagy in a fission-dependent manner but failed to induce productive mitophagy in our experimental conditions.…”

The pharmacological regulation of cellular mitophagy

“…70 On the contrary, primary human fibroblasts treated with NAM exhibit elevated levels of resting ΔΨm -however this is accompanied by a fragmentation of the mitochondrial network. 71 The effects of NAM are attributed to the activation of SIRT1 (silent information regulator T1), an NAD + -dependent deacetylase involved in the regulation of longevity. 71 By acting as its biosynthetic precursor, NAM increases the cellular availability of NAD + , which in turn activates SIRT1 and promotes mitochondrial clearance.…”

“…71 The effects of NAM are attributed to the activation of SIRT1 (silent information regulator T1), an NAD + -dependent deacetylase involved in the regulation of longevity. 71 By acting as its biosynthetic precursor, NAM increases the cellular availability of NAD + , which in turn activates SIRT1 and promotes mitochondrial clearance.…”

“…71 Mechanistically, SIRT1 could trigger mitochondrial turnover by increasing the deacetylation and subsequent activation of LC3 72 or activating the mitophagy regulator UCP2 (uncoupling protein 2) 73 . Additionally, SIRT1 has a pivotal role in cellular adaptation to hypoxic conditions by interacting with, and deacetylating, FoxO3…”

Activity of liver mitochondrial NAD+-dependent dehydrogenases of the krebs cycle in rats with acetaminophen-induced hepatitis developed under conditions of alimentary protein deficiency

“…С одной стороны, определяющими в нарушении функционирования системы биотрансформации энергии могут быть изменения на уровне структурно-функциональной организации ферментативных комплексов дыхательной цепи митохондрий [11], с другой -дефицит субстратов окисления, в первую очередь NADН. Для эффективного функционирования электронтранспортной цепи митохондрий необходимо сохранение определенного соотношения окисленных и восстановленных форм никотинамидных коферментов, определяющих скорость и направленность реакций энергообеспечения в клетке [12][13][14].…”