P47 Investigating the influence of aged-related basement membrane Laminin-332 loss in mitochondrial function
Leonor Ferreira LopesAbstract
Introduction and aims
Mitochondrial function is increasingly implicated in healthy epidermal homeostasis. From energy production, regulation of apoptosis and metabolism, to reactive oxygen species (ROS) and calcium signalling. This organelle plays a critical role in ensuring the integrity of the skin barrier by regulating proliferation and differentiation of basal keratinocytes. The integrity of this barrier is essential in protection against pathogenic entry, ultraviolet (UV) radiation and transepidermal water loss. Owing to their multifaceted role, mitochondria are one of the interdependent hallmark alterations associated with the process of ageing. In ageing skin, mitochondria are observed to have increased ROS levels, while simultaneously showing a decrease in both turnover and adenosine triphosphate production. A key alteration associated with skin ageing is the gradual reduction of essential skin basement membrane proteins, such as Laminin 332. Analysis of RNA-sequencing data highlighted that mitochondrial pathways were downregulated with the loss of laminin α-3 chain of Laminin 332.
Methods
Characterization of these altered mitochondrial pathways was conducted in laminin α-3 chain knockdown immortalized keratinocytes (sHLAMA3). Mitochondria in laminin knockdown cell display abnormal distribution and morphology.
Results
Functional assays suggest this mitochondrial altered morphology is a consequence of impaired mitochondrial quality, dynamics and mitophagy signalling pathways. An imbalance in mitochondrial fission and fusion has been identified as a potential consequence of impaired downstream integrin and focal adhesion signalling.
Conclusions
Our findings indicate that Laminin 332 loss profoundly impacts mitochondrial organization and function. Understanding the interplay between basement membrane components and mitochondrial dynamics offers new insight into skin ageing and highlights potential therapeutic targets to restore barrier function and cellular homeostasis.