Open AccessNicotinamide enhances mitochondria quality through autophagy activation in human cells
Author(s) -
Kang Hyun Tae,
Hwang Eun Seong
Publication year - 2009
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2009.00487.x
Subject(s) - autophagy , mitochondrion , biology , microbiology and biotechnology , mitophagy , mitochondrial fission , mfn1 , fis1 , mitochondrial permeability transition pore , mitochondrial apoptosis induced channel , reactive oxygen species , mitochondrial fusion , programmed cell death , inner mitochondrial membrane , apoptosis , mitochondrial dna , biochemistry , gene
Summary Nicotinamide (NAM) treatment causes a decrease in mitochondrial respiration and reactive oxygen species production in primary human fibroblasts and extends their replicative lifespan. In the current study, it is reported that NAM treatment induces a decrease in mitochondrial mass and an increase in membrane potential (ΔΨ m ) by accelerating autophagic degradation of mitochondria. In the NAM‐treated cells, the level of LC3‐II as well as the number of LC3 puncta and lysosomes co‐localizing with mitochondria substantially increased. Furthermore, in the NAM‐treated cells, the levels of Fis1, Drp1, and Mfn1, proteins that regulate mitochondrial fission and fusion, increased and mitochondria experienced dramatic changes in structure from filaments to dots or rings. This structural change is required for the decrease of mitochondrial mass indicating that NAM accelerates mitochondrial autophagy, at least in part, by inducing mitochondrial fragmentation. The decrease in mitochondria mass was attenuated by treatment with cyclosporine A, which prevents the loss of mitochondrial membrane potential by blocking the mitochondrial permeability transition, suggesting autophagic degradation selective for mitochondria with low ΔΨ m . All these changes were accompanied by and dependent on an increase in the levels of GAPDH, and are blocked by inhibition of the cellular conversion of NAM to NAD + . Taken together with our previous findings, these results suggest that up‐regulation of GAPDH activity may prolong healthy lifespan of human cells through autophagy‐mediated mitochondria quality maintenance.