Mitochondria serve as both the energy powerhouses of human cells and central arbiters of apoptosis, calcium signaling, and reactive oxygen species generation. Mitochondrial decline is a hallmark of metabolic dysfunction.
Mitochondrial Quality Control: Fission, Fusion & Mitophagy
Healthy cellular metabolism requires dynamic remodeling of the mitochondrial network:
- Mitochondrial Fusion (Mfn1, Mfn2, Opa1): Merges healthy organelles to share metabolic intermediates and complement damaged mtDNA.
- Mitochondrial Fission (Drp1, Fis1): Segregates severely damaged or depolarized mitochondrial segments.
- Mitophagy (PINK1 / Parkin Pathway): Targets dysfunctional organelles for lysosomal degradation and recycling.
NAD+ Salvage Pathway & Sirtuin Activation
Nicotinamide adenine dinucleotide (NAD+) is an indispensable coenzyme for oxidative phosphorylation and sirtuin deacylases (SIRT1, SIRT3). Age-associated CD38 upregulation depletes intracellular NAD+ pools. Clinical supplementation with precursors such as Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR) enhances mitochondrial biogenesis via PGC-1alpha activation.