생화학분자생물학회

	Name: Eun Kyung Lee ( leeek@catholic.ac.kr )
	2011-present	Assistant, Associate, Full Professor, Department of Biochemistry, The Catholic University of Korea, College of Medicine
	2008-2011	Visiting Fellow, NIH/NIA, USA
	2007-2008	Postdoctoral research fellow, Johns Hopkins Medical Institution, USA
	2000-2006	Ph.D., Department of Life Science, GIST

Mitochondrial Quantity–Quality Imbalance in Cellular Senescence: Practical Readouts and Minimal Assay Bundles

Cellular senescence is an irreversible program of cell-cycle arrest that accumulates with age, contributing to chronic inflammation and various age-related diseases. A key feature of senescence paradigms is mitochondrial dysfunction, which involves not just a single defect but a series of coordinated changes in bioenergetics, redox homeostasis, mitochondrial quality control, and organelle interaction. Senescent cells often display a “quantity–quality imbalance” in their mitochondria: while the mitochondrial mass may increase, their efficiency in oxidative phosphorylation decreases, leading to a destabilized membrane potential (ΔΨm) and elevated levels of mitochondrial reactive oxygen species (mtROS). These interrelated changes can exacerbate senescence through persistent stress signaling, impaired turnover of damaged mitochondrial components, and alterations in organelle contacts, such as those between endoplasmic reticulum (ER) and mitochondria, and between mitochondria and lysosomes. Given that these phenotypes differ depending on cell type, triggering factors, and timing, no single assay can adequately define senescence-associated mitochondrial dysfunction. In this review, we present practical, complementary strategies that include extracellular flux–based respiration profiling, ATP output measurement, ΔΨm and ROS assessments, flux-based mitophagy reporters, quantitative network imaging, and contact-site assays. We propose minimal assay bundles that allow for a thorough multidimensional analysis. By establishing standardized, orthogonal measures of mitochondrial quantity and quality, we aim to enhance mechanistic understanding and facilitate the rational evaluation of mitochondria-targeted senolytic and senomorphic therapies.


BMB Rep. 2026 Mar 9:6743. Online ahead of print.
https://pubmed.ncbi.nlm.nih.gov/41797381/