Cristae, the organized invaginations of the mitochondrial inner membrane, 
respond structurally to the energetic demands of the cell. The mechanism by 
which these dynamic changes are regulated and the consequences thereof are 
largely unknown. Optic atrophy 1 (OPA1) is the mitochondrial GTPase responsible 
for inner membrane fusion and maintenance of cristae structure. Here, we report 
that OPA1 responds dynamically to changes in energetic conditions to regulate 
cristae structure. This cristae regulation is independent of OPA1's role in 
mitochondrial fusion, since an OPA1 mutant that can still oligomerize but has no 
fusion activity was able to maintain cristae structure. Importantly, OPA1 was 
required for resistance to starvation-induced cell death, for mitochondrial 
respiration, for growth in galactose media and for maintenance of ATP synthase 
assembly, independently of its fusion activity. We identified mitochondrial 
solute carriers (SLC25A) as OPA1 interactors and show that their pharmacological 
and genetic blockade inhibited OPA1 oligomerization and function. Thus, we 
propose a novel way in which OPA1 senses energy substrate availability, which 
modulates its function in the regulation of mitochondrial architecture in a 
SLC25A protein-dependent manner.