A long-standing assumption is that mitochondrial energy capacity is uniformly regulated across all tissues in an individual. A recent study published in Life Metabolism by Martin Picard’s lab at Columbia University has discovered that mitochondrial activity and gene expression vary dramatically between organs even within the same person, suggesting that each tissue maintains its energy regulation strategy.
The study analyzed mitochondrial profiling across 22 tissues in mice and 45 human tissues using data from the genotype-tissue expression (GTEx) project. Rather than finding a consistent “high energy” or “low energy” signature across individuals, the researchers observed minimal correlation in mitochondrial function between tissues. For example, while mitochondrial function showed moderate correlation among brain regions (median r = 0.25), the correlation between brain and non-brain tissues was almost negligible (median r = 0.03). In some cases, mitochondrial function between peripheral tissues was even negatively correlated (Figure 1).
The team also identified possible mechanisms behind this diversity. Mitochondrial gene expression in each tissue was influenced by specific molecular pathways such as PGC-1α, a master regulator of mitochondrial biogenesis, and the integrated stress response (ISR). Additional regulators, such as nuclear respiratory factor 1 (NRF1), NRF2, mitochondrial transcription factor A (TFAM), and mitochondrial polymerase gamma (POLG), also showed variability in different tissues. Moreover, the study reveals that mitochondrial transcript abundance is influenced by tissue proliferation rates. Rapidly dividing tissues tend to dilute mitochondrial content, necessitating more mitochondrial biogenesis. In contrast, tissues like the brain and muscle accumulate mitochondrial transcripts without active division.
The study opens new avenues for understanding how energy metabolism contributes to disease risk and healthy aging, and underscores the importance of studying mitochondrial biology in a tissue-specific context.
DOI：10.1093/lifemeta/loaf012